Aceasta este o lista a bolilor genetice sau ereditare care au fost raportate si rasele afectate. Veti
gasi si o scurta descriere a bolii si referinte la lucrari pe aceasta tema publicate. Este precizat si
modul de transmisie, acolo unde se cunoaste. O lista completa a bolilor genetice si ereditare care
afecteaza o rasa in particular poate fi gasita aici. Va rugam sa luati in considerare ca aceste
informatii sunt destinate medicilor veterinari si ca sunt folositi termeni de specialitate, fara a fi
tradusi in limajul obisnuit.
Amyloidosis
Rase afectate: Abysinnian
Chew DJ, DiBartola SP, Boyce JT, et al. 1982. Renal amyloidosis in related Abyssinian cats.
JAVMA 181 139
Alpha-mannosidosis
Clinical signs: progressively worsening neurological signs including tremors, loss of balance,
and nystagmus from 4 to 18 weeks of age.
References Vite CH, McGowan JC, Braund KG, Drobatz KJ, Glickson JD, Wolfe JH, Haskins
ME. 2001 Histopathology, electrodiagnostic testing, and magnetic resonance imaging show
significant peripheral and central nervous system myelin abnormalities in the cat model of alphamannosidosis. J Neuropathol Exp Neurol. 60(8):817-28.
Alpha-mannosidosis is a disease caused by the deficient activity of alpha-mannosidase, a
lysosomal hydrolase involved in the degradation of glycoproteins. The disease is characterized
by the accumulation of mannose-rich oligosaccharides within lysosomes. The purpose of this
study was to characterize the peripheral nervous system (PNS) and central nervous system
(CNS) myelin abnormalities in cats from a breeding colony with a uniform mutation in the gene
encoding alpha-mannosidase. Three affected cats and 3 normal cats from 2 litters were examined
weekly from 4 to 18 wk of age. Progressively worsening neurological signs developed in
affected cats that included tremors, loss of balance, and nystagmus. In the PNS, affected cats
showed slow motor nerve conduction velocity and increased F-wave latency. Single nerve fiber
teasing revealed significant demyelination/remyelination in affected cats. Mean G-ratios of
nerves showed a significant increase in affected cats compared to normal cats. Magnetic
resonance imaging of the CNS revealed diffuse white matter signal abnormalities throughout the
brain of affected cats. Quantitative magnetization transfer imaging showed a 8%-16% decrease
in the magnetization transfer ratio in brain white matter of affected cats compared to normal cats,
consistent with myelin abnormalities. Histology confirmed myelin loss throughout the cerebrum
and cerebellum. Thus, histology, electrodiagnostic testing, and magnetic resonance imaging
identified significant myelination abnormalities in both the PNS and CNS that have not been
described previously in alpha-mannosidosis.
Anaemia - vezi Pyruvate kinase deficiency,
Ataxia - vezi Mucolipidosis type II,
Axonopathy - vezi Distal axonopathy,
Azotaemia
Rase afectate: Birman
Reference Gunn-Moore DA, Dodkin SJ, Sparkes AH. 2002 An unexpectedly high prevalence of
azotaemia in Birman cats. J Feline Med Surg. 4(3):165-6.
Blindness - vezi Mucolipidosis type II, Progressive retinal atrophy (PRA),
Cardiac defect - vezi Myocardial disease, Mucolipidosis type II, Patent ductus arteriosis,
Ventricular septal defect,
Cardiomyopathy - vezi
Cataracts - vezi Chediak-Higashi syndrome,
Cerebellar degeneration
Clinical signs: cerebellar dysfunction from the age of 7 to 8 weeks onward. Becomes
progressively worse, but not fatal, between 1 and 2.5 months.
Mode of inheritance: autosomal recessive.
Inada S, Mochizuki M, Izumo S, Kuriyama M, Sakamoto H, Kawasaki Y, Osame M. 1996 Study
of hereditary cerebellar degeneration in cats. Am J Vet Res. 57(3):296-301.
OBJECTIVE--To elucidate the nature of ataxia observed in 3 cats spanning 2 generations.
DESIGN--Experimental breeding was attempted to confirm heritability of the disease and
establish the mode of inheritance; the original 3 cats and their offspring were studied.
ANIMALS--Seven diseased cats spanning 3 generations and 11 neurologically normal cats.
PROCEDURE--Cats were examined by use of the following methods: clinical observation,
hematologic and serum biochemical examinations, neurologic examination, electrodiagnostics,
magnetic resonance imaging, lysosomal enzyme activity assay, horizontal transmission test, and
virologic and pathologic examinations. RESULTS--All kittens (1 male and 3 females) obtained
by backcrosses developed pure cerebellar dysfunction from the age of 7 to 8 weeks onward. It
became progressively worse, but not fatal, between 1 and 2.5 months. Prenatal or perinatal
infection with feline panleukopenia virus, inherited lysosomal storage diseases, including
gangliosidosis and mannosidosis, and feline hereditary neuroaxonal dystrophy were excluded.
Magnetic resonance imaging indicated that size of the cerebellum of diseased cats was markedly
reduced. Cerebellar cortical degeneration, especially with extensive destruction of Purkinje cells,
was observed microscopically. CONCLUSION--The disease was concluded to be cerebellar
degeneration of a new clinical form in cats having an autosomal recessive mode of inheritance.
CLINICAL RELEVANCE--When cerebellar dysfunction is diagnosed in a cat, hereditary
cerebellar degeneration of this type should be considered in the differential diagnosis.
Chediak-Higashi syndrome
Rase afectate: Smoke blue Persians
Clinical signs: cataracts, nystagmus
References: Collier LL, Bryan GM, Prieur DJ. 1979.
Ocular manifestations of the Chediak-Higashi syndrome in four species of animals. JAVMA 175
587-590 Ocular examinations were performed on cattle, cats, mink, and mice affected with
Chediak-Higashi syndrome (CHS). Bovine eyes were examined grossly and with an indirect
ophthalmoscope, and Schirmer tear tests were performed. Feline eyes were examined grossly as
well as with an indirect opthalmoscope and a slit lamp biomicroscope, and Schirmer tear tests
were done on them. Postrotatory nystagmus was induced and measured in clinically normal
Siamese cats, in clinically normal Persian and domestic short-haired cats, and in cats with CHS.
Mink and mouse eyes were examined grossly with focal illumination. The animals with CHS had
photophobia, pale irises, and fundic hypopigmentation associated with red fundic light
reflections. Cats with CHS also had cataracts. Spontaneous nystagmus was observed in four of
nine cats with CHS, and the duration of induced nystagmus was longer in the cats with CHS and
in Siamese cats than in clinically normal cats that were not Siamese. Tear secretion appeared to
be normal in all species of animals with CHS. The ocular manifestations of CHS in these animals
were compared with those reported in man and were found to be similar.
Collier LC, King EJ, Prieur DJ. 1985 Tapetal degeneration in cats with Chediak-Higashi
syndrome. Curr. Eye Res. 4 767-733
Kramer JW, Davis WC, Prieru DJ. 1977 The Chediak-Higashi syndrome of cats. Lab. Invest. 36
554-562
Christmas disease - vezi Haemophilia B - factor IX deficiency - Christmas disease,
Coagulopathies - vezi Hageman (coagulation factor XII) deficiency,
Rase afectate: Devon Rex
Congenital hypothyroidism
Rase afectate: Abysinnian
Jones BR, Gruffydd-Jones TJ, Sparkes AH. 1991 Congenital hypothyroidism in the cat. FAB
Bulletin 28 1 12
Congenital vestibular disease
Rase afectate: Birmans, British Cream, Burmese, Persian, Siamese
Chrisman CL. 1980 Vet. Clin. N. Amer. 10 103
deLahunta A. 1977 Veterinary Neuroanatomy and Clinical Neurology. WB Saunders,
Philadelphia 22
Evans RJ. 1985 The nervous system. In Feline Medicine and Therapeutics. (Ed.) Chandler EA,
Hilbery ADR, Gaskell CJ. 54
Corneal sequestrum - vezi Mucopolysaccharidosis I. ,
Rase afectate: Persian
Featherstone HJ, Sansom J.2004 Feline corneal sequestra: a review of 64 cases (80 eyes) from
1993 to 2000.Vet Ophthalmol. 2004 Jul-Aug;7(4):213-27.
Davies White Veterinary Specialists, Manor Farm Business Park, Higham Gobion SG3 5HR,
UK. hjf@vetspecialists.co.uk
Feline corneal sequestrum is a common condition of the feline cornea. The purpose of this study
was to provide a detailed description of the clinical features of the condition including the
response to different management options and to assess the rate of recurrence. The medical
records of 64 cases (80 eyes) of feline corneal sequestra that presented to the Animal Health
Trust from 1993 to 2000 were reviewed. Fifty-two cases were reviewed retrospectively; 12 cases
were assessed prospectively between April and September 2000 as part of a separate study. The
Persian was the most frequently encountered breed and the mean age of affected cats was 5.6
years. At initial presentation, sequestra were unilateral in 58 cats and bilateral in 6 cats, 5 of
which were Persians. Ocular discomfort and ocular discharge were common presenting signs,
occurring in 42 and 36 eyes, respectively. Seventy-four eyes were managed surgically with
keratectomy only (n = 44) or keratectomy followed by a graft procedure (n = 30). Sequestra
recurred in 16 eyes in the study. There was no significant difference in the rate of recurrence
between eyes that received a graft procedure (n = 5) and eyes that did not (n = 11) (P = 0.56).
Complications following transection of conjunctival pedicle grafts were observed. Brown to
black discoloration of noncorneal tissue and therapeutic biomaterials was observed, including
discoloration of both viable and apparently nonviable grafted conjunctival tissue, small intestinal
submucosa graft material and bandage contact lenses.
Craniofacial malformation
Rase afectate: Burmese kittens
The cranial cavity is enlarged, cerebral hemispheres duplicated, eyes missing or small, there may
be no nostrils or naval cavities.
Anon. 1982. Craniofacial malformation in Burmese kittens. Feline Practice. 12 6 32-33
Cutaneous asthenia - vezi Ehlers-Danlos Syndrome,
Deafness
Dermatosparaxis - vezi Ehlers-Danlos Syndrome,
Diabetes mellitus
Rase afectate: Burmese, domestic
Rand J. 1999 Current understanding of feline diabetes: part 1, pathogenesis.J Feline Med Surg.
1(3):143-53.
Type-1 diabetes, resulting from immune-mediated destruction of beta cells, appears to be rare in
cats. Type-2 diabetes, characterised by inadequate insulin secretion and impaired insulin action,
is the most common form of diabetes in cats. Other specific forms of diabetes constitute a
substantial minority of cases. The most common is pancreatic destruction from pancreatic
adenocarcinoma. Less frequent causes are insulin resistance from other endocrinopathies
including acromegaly. Diabetes in cats is characterised by variable loss of insulin secretory
capacity and insulin resistance. Glucose toxicity, islet amyloid-deposition, and pancreatitis
contribute to further loss of beta cells and failure of insulin secretion. A significant number of
cats undergo remission of their diabetes, usually 1-3 months after good glycaemic control is
instituted. Obesity, old age, and Burmese breed are recognised risk factors for the development
of diabetes in cats.
Rand JS, Fleeman LM, Farrow HA, Appleton DJ, Lederer R. 2004 Canine and feline diabetes
mellitus: nature or nurture? J Nutr. 134(8 Suppl):2072S-2080S.
There is evidence for the role of genetic and environmental factors in feline and canine diabetes.
Type 2 diabetes is the most common form of diabetes in cats. Evidence for genetic factors in
feline diabetes includes the overrepresentation of Burmese cats with diabetes. Environmental risk
factors in domestic or Burmese cats include advancing age, obesity, male gender, neutering, drug
treatment, physical inactivity, and indoor confinement. High-carbohydrate diets increase blood
glucose and insulin levels and may predispose cats to obesity and diabetes. Low-carbohydrate,
high-protein diets may help prevent diabetes in cats at risk such as obese cats or lean cats with
underlying low insulin sensitivity. Evidence exists for a genetic basis and altered immune
response in the pathogenesis of canine diabetes. Seasonal effects on the incidence of diagnosis
indicate that there are environmental influences on disease progression. At least 50% of diabetic
dogs have type 1 diabetes based on present evidence of immune destruction of beta-cells.
Epidemiological factors closely match those of the latent autoimmune diabetes of adults form of
human type 1 diabetes. Extensive pancreatic damage, likely from chronic pancreatitis, causes
approximately 28% of canine diabetes cases. Environmental factors such as feeding of high-fat
diets are potentially associated with pancreatitis and likely play a role in the development of
pancreatitis in diabetic dogs. There are no published data showing that overt type 2 diabetes
occurs in dogs or that obesity is a risk factor for canine diabetes. Diabetes diagnosed in a bitch
during either pregnancy or diestrus is comparable to human gestational diabetes.
Diaphragmatic hernia
Most diaphragmatic hernias are traumatic in origin (usually post road accident).
References Stork CK, Hamaide AJ, Schwedes C, Clercx CM, Snaps FR, Balligand MH. 2003
Hemiurothorax following diaphragmatic hernia and kidney prolapse in a cat.J Feline Med Surg.
5(2):91-6
A 3-year-old cat was presented with increasing dyspnoea over the past four days. Unilateral
pleural effusion was diagnosed and a modified transudate was drained several times. Surgical
exploration revealed intra-thoracic prolapse of the left kidney and partial herniation of the spleen
through a dorsal, circumferential diaphragmatic tear. Biochemical analysis of the pleural fluid
confirmed urothorax. Due to excessive fibrin deposit on the well-vascularised kidney it was
impossible to re-establish left urinary pathways. Left-sided nephrectomy and diaphragmatic
herniorrhaphy were performed. Postoperative recovery was uneventful and complete. This is the
first report of an urothorax in veterinary medical literature.
White JD, Tisdall PL, Norris JM, Malik R. 2003 Diaphragmatic hernia in a cat mimicking a
pulmonary mass. J Feline Med Surg. (3):197-201.
A seven-year-old castrated British shorthair cross cat was presented for coughing of five-weeks
duration. Thoracic radiographs and an unguided bronchoalveolar lavage showed changes
consistent with inflammatory airway disease. In addition, a soft tissue density was evident in the
thoracic films between the heart and the diaphragm. Exploratory thoracotomy demonstrated a
diaphragmatic hernia, probably congenital in origin, with incarceration of a portion of the hepatic
parenchyma. The herniated portion of liver was resected surgically and the defect in the
diaphragm closed. The cat was given a 10-day course of doxycycline post-operatively and the
cough did not recur subsequently. In retrospect, the hernia was potentially an incidental problem,
the cat's coughing being attributable to inflammatory airway disease.
Distal axonopathy
Rase afectate: Birman
Kittens of 8 to 10 weeks of age with slowly progressive posterior ataxia.
References: Moreau PM, Vallat JM, Hugon J, Leboutet MJ, Vandevelde M. 1991 Peripheral and
central distal axonopathy of suspected inherited origin in Birman cats.Acta Neu ropathol (Berl).
82(2):143-6.
Three female cats, littermates born from clinically normal parents, were examined at 8 to 10
weeks of age because of a slowly progressive posterior ataxia. Another cat from a previous litter
from the same parents suffered from similar neurological symptoms. Histopathological
examination of the nervous tissues of these animals revealed degeneration of axons and
myelinopathy in a distal distribution pattern. Both peripheral nerves and central nervous system
were involved. The central nervous system lesions were most prominent in the lateral pyramidal
tracts of the spinal cord, the fasciculi gracili of the dorsal column in the cervical spinal cord and
the cerebellar vermian white matter. In the PNS numerous degenerating nerve fibers were found
in the sciatic nerves but not in the spinal nerve roots. Our findings show that these cats were
suffering from a hereditary multisystem degeneration with a distribution pattern of the lesions
suggestive of a distal axonopathy.
Dwarfism - vezi Gangliosidosis, Mucopolysaccharidosis, Mucopolysaccharidosis VI,
Rase afectate: Domestic, Siamese
Associated with lysosomal storage disease of the liver, these cats die between 1 and 4 months of
age. Uneven litter sizes have been reported in cats infected with feline coronavirus.
Hegreberg GA, Norby DE. 1973. An inherited storage disease of cats. Fed. Proc. 32 821
Hegreberg GA, Norby DE, Hamilton MJ. 1974. Lysosomal enzyme changes in an inherited
dwarfism of cats. Fed Proc. 33 598.
Dystocia
Rase afectate: Devon Rex, Persian, Siamese-type
Gunn-Moore DA, Thrusfield MV. 1995 Feline dystocia: prevalence, and association with cranial
conformation and breed.Vet Rec. 136(14):350-3.
The litter prevalence of feline dystocia was investigated using a questionnaire survey of cat
breeders. Information was obtained on 2928 litters, from 735 queens. Dystocia was reported to
have occurred in 5.8 per cent of litters. The level of dystocia in individual breeds ranged from 0.4
per cent of litters born in a large colony of cats of mixed breeding, to 18.2 per cent of litters in
the Devon rex. Pedigree litters were at significantly higher risk than litters of cats of mixed
breeding (odds ratio: 22.6). Relatively high levels of dystocia were identified in Siamese-type,
Persian and Devon rex litters, whereas cats of mixed breeding showed a relatively low litter
prevalence. Dolicocephalic and brachycephalic types were found to have significantly higher
levels of dystocia than mesocephalic cats.
Ehlers-Danlos Syndrome
Cutaneous asthenia is a connective tissue disease primarily of dogs and cats, resembling EhlersDanlos syndrome in man. It has also been reported in a rabbit. The skin is hyperextensible, thin,
and fragile.
No breed predilection recorded so far.
References Benitah N, Matousek JL, Barnes RF, Lichtensteiger CA, Campbell KL. 2004
Diaphragmatic and perineal hernias associated with cutaneous asthenia in a cat. J Am Vet Med
Assoc. Mar 1;224(5):706-9, 698.
An 11-year-old cat was evaluated because of dyspnea. Since 11 months of age, the cat had
hyperextensibility of the skin consistent with cutaneous asthenia. Radiographic examination
revealed a diaphragmatic hernia with intestinal loops in the thorax. Electron microscopic
examination of skin specimens revealed collagen fibers of highly variable diameter, consistent
with cutaneous asthenia. The diaphragmatic hernia was surgically repaired and healed well. Four
weeks later, a left-sided perineal hernia was repaired surgically, and 4 months later, a right-sided
perineal hernia was repaired surgically and colopexy and cystopexy were performed. All surgical
procedures were successful and tissues healed well. Dermatosparaxis is a rare hereditary disorder
that commonly results in cutaneous fragility and hyperextensibility in affected animals. The
diagnosis depends on clinical findings and light and electron microscopic changes in affected
tissues. Surgical repair can be performed successfully in an affected cat, and healing of incisions
can occur without complications.
Freeman LJ, Hegreberg GA, Robinette JD, Kimbrell JT. 1989 Biomechanical properties of skin
and wounds in Ehlers-Danlos syndrome.Vet Surg. 8(2):97-102.
The biomechanical properties of wounded and nonwounded skin were studied in three dogs and
three cats affected with type I Ehlers-Danlos syndrome. Three nonaffected dogs and one
nonaffected cat served as controls. Samples of wounded skin and adjacent normal skin were
harvested at days 75, 138, 141, 144, 147, and 150. Samples were subjected to uniaxial tensile
strength testing. Tensile strength, energy absorbed, and site of failure were recorded. In the dogs
with Ehlers-Danlos syndrome, there was an increase in tensile strength in samples containing a
scar over adjacent intact skin. In nonaffected dogs, affected cats and the nonaffected cat, the
nonwounded skin samples had greater tensile strength. The energy absorbed by the skin samples
during testing was highly correlated with tensile strength.
Freeman LJ, Hegreberg GA, Robinette JD. 1989 Cutaneous wound healing in Ehlers-Danlos
syndrome.Vet Surg. 18(2):88-96.
Wound healing in five dogs and five cats affected with a connective tissue dysplasia resembling
Ehlers-Danlos syndrome of humans was compared with wound healing in 10 nonaffected
animals. Six skin incisions on the lateral aspects of the thorax and abdomen of each animal were
sutured and assessed daily for 75 days for evidence of healing. All wounds in nonaffected dogs,
affected cats, and nonaffected cats healed by first intention. Three incisions in affected dogs had
dehiscence of all or part of the incision line and healed by granulation, contraction, and
epithelialization. Biopsies taken at 3, 6, 9, 12, 15, and 75 days were compared histologically to
determine if there were any differences in rates of healing between affected and nonaffected
animals. Epidermal thickening and scab formation were noted at days 3 and 6 in both affected
and nonaffected animals. Infiltration with mononuclear cells and fibroplasia steadily increased
from day 6 to day 15 in all groups. Collagen fibril formation was evident by day 9. At day 75,
incision sites were recognized by fine, more compact collagen bundles and lack of adnexal
structures, as compared with the adjacent dermis in both affected and nonaffected animals.
Although delayed wound healing has been reported to be a complication of Ehlers-Danlos
syndrome in humans, using clinical and histologic criteria, wound healing in dogs and cats with
Ehlers-Danlos syndrome appears to be similar to nonaffected animals.
Encephalomyelopathy
Rase afectate: Birman
Onset 2-5 months of age. Hindlimb paresis and ataxia, which progresses to paralysis. Bilateral
nuclear cataracts may be present. Condition is inherited. Histopathology: spongy changes,
vacuolation and wallerian degeneration, mainly in thoracolumbar spinal cord. Diffuse lesions
also present in brain. No treatment.
Facial dysmorphia - vezi Mucolipidosis type II,
Factor (coagulation) VIII deficiency - see Hemophilia A
Factor (coagulation) IX deficiency - vezi Haemophilia B - factor IX deficiency Christmas disease,
Factor (coagulation) XII deficiency - vezi Hageman (coagulation factor XII)
deficiency,
Familial hyperlipaemia
Rase afectate: Siamese
Feline infectious peritonitis
Rase afectate: Abyssinians, Bengals, Birmans, Himalayans, Ragdolls, Rexes
References Pesteanu-Somogyi LD, Radzai C, Pressler BM. 2005 Prevalence of feline infectious
peritonitis in specific cat breeds. J Feline Med Surg.
Although known that purebreed cats are more likely to develop feline infectious peritonitis (FIP),
previous studies have not examined the prevalence of disease in individual breeds. All cats
diagnosed with FIP at a veterinary teaching hospital over a 16-year period were identified.
Breed, sex and reproductive status of affected cats were compared to the general cat population
and to mixed breed cats evaluated during the same period. As with previous studies sexually
intact cats and purebreed cats were significantly more likely to be diagnosed with FIP; males and
young cats also had a higher prevalence of disease. Abyssinians, Bengals, Birmans, Himalayans,
Ragdolls and Rexes had a significantly higher risk, whereas Burmese, Exotic Shorthairs,
Manxes, Persians, Russian Blues and Siamese cats were not at increased risk for development of
FIP. Although additional factors doubtlessly influence the relative prevalence of FIP, this study
provides additional guidance when prioritizing differentials in ill purebreed cats.
Feline leukocyte antigen DRB restricted polymorphism
Rase afectate: Burmese
Reference Kennedy LJ, Ryvar R, Brown JJ, Ollier WE, Radford AD. 2003 Resolution of
complex feline leukocyte antigen DRB loci by reference strand-mediated conformational
analysis (RSCA). Tissue Antigens. 62(4):313-23.
The DRB genes of the domestic cat are highly polymorphic. Studies based on clonal sequence
analysis have suggested the existence of two distinct loci within individual animals and good
evidence for 24 distinct FLA-DRB alleles. This variability, the complexity of clonal sequence
analysis and its susceptibility to PCR-induced artefacts has represented a bottleneck to further
progress. In this study we have applied reference strand-mediated conformational analysis
(RSCA) to FLA-DRB. This protocol has been shown to be highly reproducible. Using five
reference strands including two derived from non-domestic felines, we could distinguish 23
FLA-DRB alleles. We used RSCA to explore genetic polymorphism of FLA-DRB in 71 cats
including 31 for which clonal sequence analysis was also available. On average, RSCA
identified 0.9 more alleles within cats than clonal sequence analysis. Reference strand-mediated
conformational analysis was also able to identify animals containing new alleles that could be
targeted for sequence analysis. Analysis of allele patterns showed clear evidence for different
allele distributions between breeds of cats, and suggested the Burmese breed may have highly
restricted FLA-DRB polymorphism. Results from two families provided clear evidence for
variation in the number of DRB genes on different haplotypes, with some haplotypes carrying
two genes and some containing three. This study highlights the utility of RSCA for the resolution
of complex amplicons containing up to six distinct alleles. A simple, rapid method for
characterizing FLA-DRB makes possible studies on vaccine response and
susceptibility/resistance to viral infections, which are a significant clinical problem in cats.
Flat-chested kittens
Rase afectate: Burmese
Gastric adenocarcinoma
Rase afectate: Persian
Clinical signs: vomiting, hematemesis, intermittent melena, and weight loss
Reference Dennis MM, Bennett N, Ehrhart EJ. 2006 Gastric adenocarcinoma and chronic
gastritis in two related Persian cats. Vet Pathol. 43(3):358-62
Gastritis
Gangliosidosis
Rase afectate: Domestic shorthair, Korat
Clinical signs: slowly progressive neurological dysfunction, premature thymic involution,
stunted growth, and premature death. Circulating monocytes and lymphocytes showed the
presence of single or multiple empty vacuoles.
Mode of inheritance: autosomal, recessively inherited.
Gingivitis
Rase afectate: Abysinnian, Persian
Clinical signs: hyperemic, proliferative gingivitis Gingivitis-periodontitis - feline juvenile-onset
DSH, Maine Coon, Siamese Small stature and have a history of being "sickly" as kittens, often
with chronic upper respiratory disease. Initial oral signs occur just before eruption of adult teeth.
Gingival recession, pocketing, bone loss and furcation exposures are common. Lesions may be
localized or generalized and often first seen in the central lower incisor area. Reference Williams
CA, Aller MS. 1992 Gingivitis/stomatitis in cats. Veterinary Clinics of North America. 22 6
1361 - 1383
Glaucoma
Rase afectate: Burmese
References Hampson EC, Smith RI, Bernays ME. 2002 Primary glaucoma in Burmese cats.Aust
Vet J. 80(11):672-80.
OBJECTIVE: To document the clinical signs and management of primary glaucoma in Burmese
cats. DESIGN: A retrospective study of six affected Burmese cats, from 1996 to 2001. Procedure
Six Burmese cats diagnosed with primary glaucoma were managed over periods varying from 3
months to 4.5 years. Clinical details were obtained from practice records. Gonioscopic
examination of the drainage or iridocorneal angle in eyes of these affected cats was made.
RESULTS: Six desexed female Burmese cats (ages 7.0 to 10.5 years) presented with complaints
of either unilateral (n = 4) or bilateral (n = 2) red eye, dilated pupil or enlarged eye. In one of the
affected cats, one eye had been enucleated prior to the commencement of the study, thus a total
of 11 eyes were examined. Clinically, all affected eyes (n = 8) had injected episcleral blood
vessels and elevated intraocular pressure. Gonioscopy revealed the presence of nine narrow and
two closed iridocorneal angles. Medical therapy included topical 2% dorzolamide (n = 8), 0.5%
timolol maleate (n = 1), 0.005% latanoprost (n = 1) and 0.5-1.0% prednisolone acetate (n = 8).
Surgery was performed in six eyes using either diode laser (n = 5) and/or cryothermy (n = 2) and
one eye was eviscerated, with implantation of a prosthesis. With therapy, five affected eyes
maintained vision and normal intraocular pressure, one eye remained blind with normal
intraocular pressure, one eye remained blind with elevated intraocular pressure and one eye was
eviscerated. CONCLUSIONS: The Burmese cat may be predisposed to primary narrow-angle
glaucoma. Early diagnosis and continuous antiglaucoma therapy can help control intraocular
pressure and maintain vision.
Glycogen storage diseases
Rase afectate: Norwegian Forest Cats
Reference Fyfe JC, Giger U, Van Winkle TJ, Haskins ME, Steinberg SA, Wang P, Patterson
DF.1992
Glycogen storage disease type IV: inherited deficiency of branching enzyme activity in
cats.Pediatr Res.32(6):719-25. Glycogen storage disease type IV due to branching enzyme
deficiency was found in an inbred family of Norwegian forest cats, an uncommon breed of
domestic cats. Skeletal muscle, heart, and CNS degeneration were clinically apparent and
histologically evident in affected cats older than 5 mo of age, but cirrhosis and hepatic failure,
hallmarks of the human disorder, were absent. Beginning at or before birth, affected cats
accumulated an abnormal glycogen in many tissues that was determined by histochemical,
enzymatic, and spectral analysis to be a poorly branched alpha-1,4-D-glucan. Branching enzyme
activity was less than 0.1 of normal in liver and muscle of affected cats and partially deficient
(0.17-0.75 of normal) in muscle and leukocytes of the parents of affected cats. These data and
pedigree analysis indicate that branching enzyme deficiency is a simple autosomal recessive trait
in this family. This is the first reported animal model of human glycogen storage disease type IV.
A breeding colony derived from a relative of the affected cats has been established.
Haemophilia A (factor VIII deficiency)
Haemophilia B - factor IX deficiency - Christmas disease
Rase afectate: British shorthair, Domestic
Clinical signs: regenerative anaemia, haemorrhage, subcutaneous haematomas, prolonged
bleeding times, shifting lameness.
References Dillon AR, Boudreaux MK. 1988 Combined factors IX and XII deficiencies in a
family of cats.J Am Vet Med Assoc. 193(7):833-4.
Combined factors IX and XII deficiencies were detected in a family of cats in which 2 male
kittens had bleeding diathesis. The combination of factors IX and XII deficiencies in one male
kitten did not appear to exacerbate bleeding when compared with a sole deficiency of factor IX
in its male sibling. Neutering of carrier females and affected males was recommended. Blood
transfusions before castration of affected males was advised.
Goree M, Catalfamo JL, Aber S, Boudreaux MK. 2005 Characterization of the mutations causing
hemophilia B in 2 domestic cats.J Vet Intern Med. 2005 Mar-Apr;19(2):200-4.
The purpose of the present study was to determine the normal sequence for the gene encoding
factor IX in cats and to characterize the genetic basis for hemophilia B in 2 unrelated male,
domestic, mixed-breed cats. Genomic DNA sequence for the entire coding region of the factor
IX gene was determined in the affected cats and compared to the sequence obtained from a
healthy cat. The factor IX gene in cats encodes a mature protein consisting of 420 amino acids,
unlike genes in humans and dogs that encode 415 and 413 amino acid proteins, respectively.
Affected cat 1 had a single nucleotide change in exon 8 at the 1st nucleotide position of the
codon encoding an arginine (CGA to TGA) at amino acid position 338. This mutation would be
predicted to result in the appearance of a premature stop codon in the portion of the gene
encoding much of the catalytic domain of the protein. Affected cat 2 had a single nucleotide
change in exon 4 at the 2nd nucleotide position of the codon encoding amino acid 82 (TGT to
TAT), which would be predicted to result in the substitution of a tyrosine for a cysteine. This
substitution would likely result in disruption of a disulfide bond crucial to normal protein
structure and function. This study represents the 1st time hemophilia B has been characterized at
the molecular level in cats.
Lutze G, Kutschmann K, Furst K, Schneppenheim R. 2005 Hemophilia B (factor IX deficiency)
with concomitant factor XII degradation in a male crossbreed cat. Berl Munch Tierarztl
Wochenschr. 118(5-6):255-60.
A male cat suffered from a severe haemorrhagic disorder manifesting as deep, partly infected
cutaneous haematomas, enhanced and prolonged bleeding after injuries and subsequent lameness
at several occasions. Bleeding resulted in severe anaemia with haematocrit falling to as low as
0.10 L/L. Haemophilia B was diagnosed based on factor IX deficiency with a functional residual
activity of 5% and factor IX antigen of 8%, respectively. Additionally, factor XII activity was
reduced to 32% of normal. The mutation 31217G==>A in exon 8 of the factor IX gene,
predicting the amino acid exchange G366R was identified as the cause of moderate factor IX
deficiency. This is the first mutation identified in cats with haemophilia B. Treatment was
limited to local therapy and palliation, insufficient to prevent lethal outcome due to severe
anaemia.
Maggio-Price L, Dodds WJ. 1993 Factor IX deficiency (hemophilia B) in a family of British
shorthair cats.J Am Vet Med Assoc. 203(12):1702-4.
This report describes the clinical findings of a British shorthair cat with hemophilia B, the family
pedigree surrounding the case, and how this disorder can be perpetuated in rare breeds of cats
that may be inbred by necessity. Young cats with histories of bleeding episodes following
elective or other surgical procedures, periodic shifting lamenesses, or the development of
subcutaneous hematomas should be suspect for an inherited coagulation disorder. Hemophilia A
(factor VIII deficiency) or hemophilia B (factor IX deficiency) are the most likely causes,
although other inherited bleeding disorders also have been recognized in cats.
Hageman (coagulation factor XII) deficiency
Rase afectate: Domestic
Mode of inheritance: autosomal recessive
References Dillon AR, Boudreaux MK. 1988
Combined factors IX and XII deficiencies in a family of cats.J Am Vet Med Assoc. 193(7):8334. Combined factors IX and XII deficiencies were detected in a family of cats in which 2 male
kittens had bleeding diathesis. The combination of factors IX and XII deficiencies in one male
kitten did not appear to exacerbate bleeding when compared with a sole deficiency of factor IX
in its male sibling. Neutering of carrier females and affected males was recommended. Blood
transfusions before castration of affected males was advised.
Kier AB, Bresnahan JF, White FJ, Wagner JE. The inheritance pattern of factor XII (Hageman)
deficiency in domestic cats.Can J Comp Med. 1980 Jul;44(3):309-14.
Measurements of coagulation factor XII levels in F1 progeny of a cat having factor XII
deficiency revealed an autosomal recessive pattern similar to that reported in humans (Hageman
trait). A study of the pedigree of the colony revealed that F1 kittens had approximately 50%
factor XII activity while kittens produced by backcrossing with an F1 progeny possessed an
average of 50% and a less than 2% factor XII activity in an approximate 1:1 ratio. Kittens having
an average of 50% factor XII activity were postulated heterozygous for the trait while progeny
with less than 2% activity were considered genetically homozygous.
Heart defect - vezi Ventricular septal defect,
Heart disease - vezi Mucolipidosis type II, Myocardial disease, Patent ductus arteriosis,
Ventricular septal defect,
Hernia - vezi Ehlers-Danlos Syndrome,
Hernias can be secondary to Ehlers-Danlos syndrome.




Diaphragmatic hernia
Hiatus hernia
Perineal hernia
Umbillical hernia
Hip dysplasia
Clinical signs: hindlimb lameness, history of constipation
References Keller GG, Reed AL, Lattimer JC, Corley EA. 1999 Hip dysplasia: a feline
population study.Vet Radiol Ultrasound. 40(5):460-4.
The study population consisted of cats presented to the University of Missouri-Columbia
Veterinary Medical Teaching Hospital from January 1, 1991 through December 31, 1995.
Ventrodorsal radiographs including the pelvic region were evaluated for radiographic evidence
of hip dysplasia. Each radiograph was evaluated independently by three board-certified
veterinary radiologists and a consensus normal of dysplastic evaluation was determined. There
were 684 cats from 12 breeds. The data derived from this study indicate the frequency of feline
hip dysplasia in this population to be about 6.6% (45/684) and that the incidence appears to be
breed dependent. Also, the radiographic appearance of hip dysplasia in cats is different than in
dogs. A shallow acetabulum with remodeling and proliferation involving the cranio-dorsal
acetabular margin were the most common radiographic signs. Minimal remodeling of the
femoral neck was seen.
Patsikas MN, Papazoglou LG, Komninou A, Dessiris AK, Tsimopoulos G. 1998 Hip dysplasia in
the cat: a report of three cases. J Small Anim Pract. 39(6):290-4.
Hip dysplasia was diagnosed in three cats. Two were presented with a history of hindlimb
lameness and the other had a history of constipation. All were confined for two weeks and
showed considerable clinical improvement. At follow-up examination the cats were free of
clinical signs despite the deterioration in the radiological appearance of their hips. Luxation or
subluxation of the hips, insufficient development of the craniolateral acetabular edges, loss of the
arched shape of the cranial subchondral acetabular bones, shallow acetabula and secondary
degenerative changes on the femoral heads and necks were the main radiological findings in the
affected cats.
Hypokalaemic myopathy
Rase afectate: Burmese
Clinical signs: periodic muscle weakness and cervical ventroflexion, onset can be as early as 10
weeks old.
Mode of inheritance: homozygote recessive
References Gaschen F, Jaggy A, Jones B. 2004 Congenital diseases of feline muscle and
neuromuscular junction. J Feline Med Surg. (6):355-66.
Although muscle diseases occur relatively rarely in cats, a number of congenital feline
myopathies have been described over the last 20 years and are reviewed in this paper. Some of
them have been reported exclusively in specific breeds, including the hypokalaemic myopathy of
Burmese cats, type IV glycogen storage disease in Norwegian Forest cats, or the myopathy of
Devon Rex. Other congenital disorders of muscle and neuromuscular junction such as myotonia
congenita, dystrophin-deficient hypertrophic feline muscular dystrophy, laminin alpha2
deficiency, or congenital myasthenia gravis may occur in any cat. A systematic approach is
essential in order to efficiently obtain a timely diagnosis in cats showing signs of muscle disease.
After a thorough clinical examination, this approach includes blood analyses (eg, serum
concentration of muscle enzymes), electrophysiology where available (electromyography, nerve
conduction studies), and sampling of muscle biopsies for histological, histochemical and
immunohistochemical evaluation. When available, detection of healthy carriers of these genetic
disorders is important to eliminate the gene mutations from breeding families. Clinicians
regularly receiving feline patients must have a good knowledge of congenital feline myopathies
and the features which enable a diagnosis to be made and prognosis given. Besides preserving or
restoring the well-being of the myopathic patient, rapid and efficient information and counselling
of the breeders are of central importance in order to prevent the recurrence of the problem in
specific breeding lines.
Jones BR, Swinney GW, Alley MR. 1988 Hypokalaemic myopathy in Burmese kittens.N Z Vet
J. 36(3):150-1.
Since 1984 there have been a number of reports of polymyopathy in cats characterised by
clinical signs of generalised weakness of the limb and neck muscles. In most of these cases the
polymyopathy was associated with a concurrent hypokalaemia. A direct causal relationship was
not established in one series of cases, but in the second excessive urine potassium loss with
decreased potassium intake was suspected. It was concluded by these authors that increased
urinary potassium secretion was a basic response to renal dysfunction in cats. Periodic muscle
weakness has also been recognised in young Burmese kittens (10 weeks to one year) which was
characterised by ventroflexion of the neck, elevated creatinine phosphokinase (CPK) activity and
intermittent hypokalaemia.
Lantinga E, Kooistra HS, van Nes JJ. 1998 Periodic muscle weakness and cervical ventroflexion
caused by hypokalemia in a Burmese cat. Tijdschr Diergeneeskd. 123(14-15):435-7.
A 2-year-old female Burmese cat was referred to the University Hospital of Companion Animals
of Utrecht University because of periodic muscle weakness and cervical ventroflexion.
Laboratory examinations revealed hypokalemia. The combination of breed, clinical signs and
hypokalemia warranted the diagnosis of 'periodic hypokalemic myopathy', a homozygote
recessive hereditary disease in Burmese cats. Potassium supplementation resulted in complete
disappearance of the signs. Possible causes of hypokalemia in the cat are discussed.
Laminin alpha2 deficiency - vezi Muscular dystrophy,
Lipoprotein lipase deficiency
Clinical signs: fasting hyperlipaemia, lipaemia retinalis, peripheral neuropathies and
subcutaneous xanthomas
References Johnstone AC, Jones BR, Thompson JC, Hancock WS. 1990 The pathology of an
inherited hyperlipoproteinaemia of cats. J Comp Pathol. 102(2):125-37
The gross and histological features of congenital lipoprotein lipase deficiency are described in
eight cats. The main histological features could be directly related to the presence of the
chylomicronaemia. They consisted of lipid accumulation within clear vacuoles or ceroid
accumulation within residual bodies in parenchymatous organs such as the liver, spleen, lymph
nodes, kidney and adrenal gland. Xanthomata were seen in various sites, probably arising either
from frank haemorrhage or the leakage of lipid-rich plasma perivascularly. As in human
lipoprotein lipase deficiency there was no evidence of the formation of atherosclerotic plaques.
Focal degenerative changes were, however, present within arteries and this may indicate blood
vessel weakness and explain the tendency to haemorrhage and xanthomata/granulomata
formation. The degeneration and fibrous replacement of glomeruli and nephrons possibly arises
from pressure necrosis of adjacent xanthomata and alterations in renal blood flow.
Jones BR, Wallace A, Harding DR, Hancock WS, Campbell CH 1983.Occurrence of idiopathic,
familial hyperchylomicronaemia in a cat. Vet Rec. 112(23):543-7.
Primary hyperlipoproteinaemia (hyperchylomicronaemia with slight very low density lipoprotein
elevation) is described in two related male cats. Fasting hyperlipaemia, lipaemia retinalis and
subcutaneous xanthomas were detected on clinical examination. In one cat lipoprotein lipase
activity measured after heparin activation was significantly reduced compared to the response in
a normal cat. The lipid and protein concentration in each of the lipoprotein classes and the
lipoprotein distribution of the two hyperlipaemic cats, two normolipaemic relations and 16
normolipaemic adult cats were determined. Plasma cholesterol and triglyceride levels were
elevated in the hyperlipaemic cats with the major proportion of triglyceride and cholesterol being
present in chylomicrons whereas in normolipaemic cats the majority of triglyceride was
contained in very low density lipoprotein. High density lipoprotein was the predominant lipid
carrier in both the normolipaemic and the hyperlipaemic cats but the protein content in
chylomicrons was elevated in the two affected cats. The lipoprotein distribution in normal cats in
this study agrees with previously reported values. The hyperlipaemic cats showed many of the
features of familial lipoprotein lipase deficiency (type I hyperlipoproteinaemia, exogenous
chylomicronaemia) which is an inherited disease in man.
Jones BR, Johnstone AC, Cahill JI, Hancock WS. 1986 Peripheral neuropathy in cats with
inherited primary hyperchylomicronaemia.Vet Rec. 1986 Sep 13;119(11):268-72.
Primary hyperlipoproteinaemia (hyperchylomicronaemia) with a slight increase in very low
density lipoprotein) is described in 20 cats. Fasting hyperlipaemia, lipaemia retinalis and
peripheral neuropathies were the most frequently detected clinical signs. The disease is thought
to be inherited as an autosomal recessive trait but the exact mode of inheritance has not been
determined. Affected cats showed reduced lipoprotein lipase activity measured after heparin
activation compared with the response in normal cats. Plasma triglyceride and cholesterol were
increased in all the cats with the major proportion of triglyceride and cholesterol being present in
chylomicrons. The peripheral nerve lesions were caused by compression of nerves by lipid
granulomata. It is probable that the lipid granulomata result from trauma because the nerves most
often affected were at sites like the spinal foraminae where they were susceptible to trauma.
Thompson JC, Johnstone AC, Jones BR, Hancock WS. 1989 The ultrastructural pathology of
five lipoprotein lipase-deficient cats.J Comp Pathol. 101(3):251-62.
The ultrastructural pathology of cats suffering from familial lipoprotein lipase deficiency is
described. There were large numbers of lipid vacuoles within hepatocytes, epithelial cells of the
proximal convoluted tubule of kidney and macrophages of the liver, spleen and lymph node. The
older cats tended to have larger quantities of ceroid within hepatocytes and macrophages, and all
stages of development of ceroid were observed. Chylomicron emboli were seen within the
glomerular capillaries and interlobular blood vessels. There was podocyte foot fusion and
thickening of basement membranes of glomeruli, Bowman's capsule and some proximal
convoluted tubules, similar to that seen in diabetes mellitus. These changes represent a nonspecific reaction of the kidney to noxious insults such as hypoxia caused by emboli.
Transformation of smooth muscle cells from a contractile to a synthetic state was seen in the
splenic trabeculae and, to a lesser extent, in blood vessels. Dilatations of the nuclear membrane
of the lymphocytes were noted, the significance of which is unknown.
Lysosomal storage disease
Hegreberg GA, Norby DE, Hamilton MJ. 1974. Lysosomal enzyme changes in an inherited
dwarfism of cats. Fed Proc. 33 598.
Mannosidosis
Vacuolation of lymphocytes and monocytes.
Manx
Robinson R. 1993 Expressivity of the Manx gene in cats. J Hered. 1993 May-Jun;84(3):170-2.
New genetic data are presented which indicate that the assortment data for the mutant Manx
gene, M, does not depart from normal expectation and does not enjoy a selective advantage at
some stage of gametogenesis, as has been hypothesized. The variable expression of Manx
taillessness is a remarkable and consistent feature of the Manx syndrome, encompassing the
posterior skeleton, neural organization, and growth of soft tissues. The expression is partly
genetic in origin, and the heritability is estimated to be in the region of h2 = 0.40 +/- 0.11.
Mucolipidosis type II
Rase afectate: Domestic
Clinical signs: clinical features in affected kittens were observed from birth in some kittens,
others are months old when presented. Clinical signs include failure to thrive, abnormal facial
features, retarded growth, behavioral dullness, facial dysmorphia, diffuse retinal degeneration
leading to blindness by 4 months of age, ataxia, progressive hindlimb paresis, upper respiratory
signs, cardiac failure. Radiographic lesions included metaphyseal flaring, radial bowing, joint
laxity, and vertebral fusion.
Mode of inheritance: autosomal recessive
References Hubler M, Haskins ME, Arnold S, Kaser-Hotz B, Bosshard NU, Briner J, Spycher
MA, Gitzelmann R, Sommerlade HJ, von Figura K. 1996 Mucolipidosis type II in a domestic
shorthair cat. J Small Anim Pract. 1996 Sep;37(9):435-41.
A seven-month-old, female domestic shorthair cat was presented to the Veterinary Teaching
Hospital, University of Zurich, with abnormal facial features, retarded growth and progressive
hindlimb paresis. On physical examination the cat had a flat, broad face with hypertelorism,
frontal bossing, small ears and thickened upper and lower eyelids. The corneas of both eyes were
clear and the pupils were dilated. The skin was generally thickened, most prominently on the
dorsal aspect of the neck. Radiography of the entire skeleton revealed a severely deformed spinal
column, bilateral hip luxation with hip dysplasia, an abnormally shaped skull and generalised
decreased bone opacity. The clinical features and radiographic changes were suggestive of
mucopolysaccharidosis. The toluidine blue spot test on a urine sample, however, was negative
for glycosaminoglycans. Further biochemical investigations revealed a deficiency of the enzyme
N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase, EC 2.7.8.17) in
peripheral leukocytes and an elevation of many lysosomal enzymes in the serum of the cat which
is diagnostic for mucolipidosis type II. Histology and electron microscopy of different tissues are
briefly summarised. The findings of this cat, the first reported case of mucolipidosis type II are
compared with other similar storage diseases described in the cat.
Mazrier H, Van Hoeven M, Wang P, Knox VW, Aguirre GD, Holt E, Wiemelt SP, Sleeper MM,
Hubler M, Haskins ME, Giger U. 2003 Inheritance, biochemical abnormalities, and clinical
features of feline mucolipidosis II: the first animal model of human I-cell disease. J Hered.
94(5):363-73.
Mucolipidosis II (ML II), also called I-cell disease, is a unique lysosomal storage disease caused
by deficient activity of the enzyme N-acetylglucosamine-1-phosphotransferase, which leads to a
failure to internalize enzymes into lysosomes. We report on a colony of domestic shorthair cats
with ML II that was established from a half-sibling male of an affected cat. Ten male and 9
female kittens out of 89 kittens in 26 litters born to clinically normal parents were affected; this
is consistent with an autosomal recessive mode of inheritance. The activities of three lysosomal
enzymes from affected kittens, compared to normal adult control cats, were high in serum (11-73
times normal) but low in cultured fibroblasts (9-56% of normal range) that contained inclusion
bodies (I-cells), reflecting the unique enzyme defect in ML II. Serum lysosomal enzyme
activities of adult obligate carriers were intermediate between normal and affected values.
Clinical features in affected kittens were observed from birth and included failure to thrive,
behavioral dullness, facial dysmorphia, and ataxia. Radiographic lesions included metaphyseal
flaring, radial bowing, joint laxity, and vertebral fusion. In contrast to human ML II, diffuse
retinal degeneration leading to blindness by 4 months of age was seen in affected kittens. All
clinical signs were progressive and euthanasia or death invariably occurred within the first few
days to 7 months of life, often due to upper respiratory disease or cardiac failure. The clinical
and radiographic features, lysosomal enzyme activities, and mode of inheritance are homologous
with ML II in humans. Feline ML II is currently the only animal model in which to study the
pathogenesis of and therapeutic interventions for this unique storage disease.
Mucopolysaccharidosis
Rase afectate: Siamese
The mucopolysaccharidoses (MPS) are inherited metabolic disorders resulting from the defective
catabolism of glycosaminoglycans.
Cowell KR, Jezyk PF, Haskins ME, Patterson DF. 1976 Mucopolysaccharidosis in a cat. J Am
Vet Med Assoc. 169(3):334-9.
A young adult female Siamese cat born of a mother-son mating was referred because of
dwarfism, facial abnormalities, severe skeletal deformities, multifocal neurologic deficits, and
retinal atrophy. Cats of similar appearance had been observed in a previous litter of the same
parents. Metachromatic inclusion bodies were demonstrated in circulating leukocytes. The urine
contained a high concentration of mucopolysaccharide, as detected by the toluidine blue spot
test. The uronic acid content of the cetylpyridinium chloride-precipitable mucopolysaccharide in
the urine was 17 times greater than that in the urine from a control cat of the same age and breed.
Mucopolysaccharidosis I.
Clinical signs: corneal clouding
Reference Kakkis ED, Schuchman E, He X, Wan Q, Kania S, Wiemelt S, Hasson CW, O'Malley
T, Weil MA, Aguirre GA, Brown DE, Haskins ME. 2001 Enzyme replacement therapy in feline
mucopolysaccharidosis I. Mol Genet Metab. 72(3):199-208.
Enzyme replacement therapy (ERT) has long been considered an approach to treating lysosomal
storage disorders caused by deficiency of lysosomal enzymes. ERT is currently used to treat
Gaucher disease and is being developed for several lysosomal storage disorders now that
recombinant sources of the enzymes have become available. We have continued development of
ERT for mucopolysaccharidosis I (MPS I) using the feline model. Recombinant alpha-Liduronidase was administered intravenously at low dose (approximately 0.1 mg/kg or 25,000
units/kg) to four cats and high dose (0.5 mg/kg or 125,000 units/kg) to two cats on a weekly
basis for 3- or 6-month terms. Clinical examinations showed distinct clearing of corneal clouding
in one cat although clinical effects in the others were not evident. Biochemical studies of the cats
showed that the enzyme was distributed to a variety of tissues although the liver and spleen
contained the highest enzyme activities. Glycosaminoglycan storage was decreased in liver and
spleen, and the histologic appearance improved in liver, spleen, and renal cortex. Enzyme was
not consistently detected in cerebral cortex, brainstem, or cerebellum and the histologic
appearance and ganglioside profiles did not improve. A variety of other tissues showed low
variable uptake of enzyme and no distinct improvement. IgG antibodies to alpha-L-iduronidase
were observed in five cats with higher titers noted when higher doses were administered. Mild
complement activation occurred in three cats. Enzyme replacement therapy was effective in
reversing storage in some tissues at the biochemical and histologic level in MPS I cats but an
improved tissue distribution and prevention of a significant immune response could make the
therapy more effective.
Mucopolysaccharidosis VI
Rase afectate: Siamese
Clinical signs: dwarfism, degenerative joint disease, skeletal deformities, facial dysmorphia due
to epiphyseal dysplasia,degenerative joint disease, corneal clouding, and abnormal leukocyte
inclusions.
References and abstracts. Crawley AC, Muntz FH, Haskins ME, Jones BR, Hopwood JJ. 2003
Prevalence of mucopolysaccharidosis type VI mutations in Siamese cats.J Vet Intern Med.
17(4):495-8.
Mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease, is one of the more
prevalent inherited diseases in cats and is commonly found in cats with Siamese ancestry. The
prevalence of 2 known MPS VI mutations in cats was investigated in 101 clinically normal
Siamese cats, in 2 cats with clinical signs of MPS VI, and in 202 cats from 4 research colonies.
The mutation L476P which causes a severe clinical phenotype, was present on both alleles in the
known MPS VI cats from Italy and North America and was present in all research colonies that
originated from North America. However, LA76P was not detected in the Siamese population
screened. In contrast, the mutation D520N, which causes a mild clinical phenotype, was
identified in 23 of 202 (11.4%) alleles tested in Siamese cats from 3 continents, 2 of which were
homozygous for D520N. Thus, the D520N mutation was widespread, and it is likely that cats
inheriting both mutations (LA76P/D520N compound heterozygotes) would be in the general
Siamese population, particularly in North America. Practitioners should note the high incidence
of degenerative joint disease in these animals.
Crawley AC, Yogalingam G, Muller VJ, Hopwood JJ. 1998 Two mutations within a feline
mucopolysaccharidosis type VI colony cause three different clinical phenotypes. J Clin Invest.
101(1):109-19
Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disease caused by a deficiency
of N-acetylgalactosamine-4-sulfatase (4S). A feline MPS VI model used to demonstrate efficacy
of enzyme replacement therapy is due to the homozygous presence of an L476P mutation in 4sulfatase. An additional mutation, D520N, inherited independently from L476P and recently
identified in the same family of cats, has resulted in three clinical phenotypes. L476P
homozygotes exhibit dwarfism and facial dysmorphia due to epiphyseal dysplasia, abnormally
low leukocyte 4S/betahexosaminidase ratios, dermatan sulfaturia, lysosomal inclusions in most
tissues including chondrocytes, corneal clouding, degenerative joint disease, and abnormal
leukocyte inclusions. Similarly, D520N/D520N and L476P/D520N cats have abnormally low
leukocyte 4S/betahexosaminidase ratios, mild dermatan sulfaturia, lysosomal inclusions in some
chondrocytes, and abnormal leukocyte inclusions. However, both have normal growth and
appearance. In addition, L476P/D520N cats have a high incidence of degenerative joint disease.
We conclude that L476P/D520N cats have a very mild MPS VI phenotype not previously
described in MPS VI humans. The study of L476P/D520N and D520N/ D520N genotypes will
improve understanding of genotype to phenotype correlations and the pathogenesis of skeletal
dysplasia and joint disease in MPS VI, and will assist in development of therapies to prevent
lysosomal storage in chondrocytes.
Ho TT, Maguire AM, Aguirre GD, Surace EM, Anand V, Zeng Y, Salvetti A, Hopwood JJ,
Haskins ME, Bennett J. 2002 Phenotypic rescue after adeno-associated virus-mediated delivery
of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI. J Gene Med.
4(6):613-21.
BACKGROUND: Mucopolysaccharidosis VI (MPS VI), due to recessively inherited 4-sulfatase
(4S) deficiency, results in lysosomal storage of dermatan sulfate in numerous tissues. Retinal
involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine
whether recombinant adeno-associated virus (AAV)-mediated delivery of 4S would reverse the
RPE pathology seen in MPS VI cats. METHODS: AAV.f4S, containing the feline 4S cDNA,
was delivered unilaterally to eyes of affected cats by subretinal or intravitreal injection.
Contralateral eyes received AAV with the green fluorescent protein (GFP) reporter gene as
control. At 2-11 months post-injection, the cats were sacrificed and the treatment effects were
evaluated histologically. RESULTS: By ophthalmoscopy and histological analyses, GFP was
evident as early as 4 weeks and persisted through the latest time point (11 months). Untreated
and AAV.GFP-treated diseased retinas contained massively hypertrophied RPE cells secondary
to accumulation of dilated lysosomal inclusions containing dermatan sulfate. MPS VI eyes
treated subretinally with AAV.f4S had minimal RPE cell inclusions and, consequently, were not
hypertrophied. CONCLUSIONS: AAV-mediated subretinal delivery of f4S provided correction
of the disease phenotype in RPE cells of feline MPS VI, supporting the utility of AAV as a
vector for the treatment of RPE-specific as well as lysosomal storage diseases.
Macri B, Marino F, Mazzullo G, Trusso A, De Maria R, Amedeo S, Divari S, Castagnaro M.
2002 Mucopolysaccharidosis VI in a Siamese/short-haired European cat. J Vet Med A Physiol
Pathol Clin Med. Oct;49(8):438-42.
A 3-year-old Siamese/short-haired European cat was referred for clinical disease characterized
by dwarfism, facial dysmorphia, paralysis, small and curled ears, corneal clouding and large
areas of alopecia. X-ray examination showed multiple bone dysplasia. On the basis of clinical
features a form of mucopolysaccharidosis was suspected. The cat, killed at the owner's request,
presented several severe skeletal deformities such as long caudal limbs, enlarged thorax with
sunken breastbone, vertebral ankylosis in many spinal segments and visceral involvement.
Histologically, the cat showed diffuse vacuolization and enlargement of cells in cartilage, bone
and visceral organs. Ultrastructurally, membrane-bound vacuoles were filled with fibrillar and
fluffy-material or concentrically whorled lamellae. Arylsulphatase B activity was 3.24 nm/mg/h
in the affected cat and 30.6 in a normal age-matched control (NC). The L-iduronidase activity
was slightly increased. Quantitation of total glycosaminoglycans (GAGs) revealed a 4.5-fold
increase in the affected cat as compared with NC, while electrophoretic run of specific GAGs
[chondroitin sulphate (CA); hyaluronan (HA); heparan sulphate (HS); dermatan sulphate (DS);
keratan sulphate (KS)] performed on a cellulose acetate sheet, showed a striking increase in the
DS band. On densitometric analysis of the electrophoretic run stained with Alcian Blue 8GX, the
absorption of DS was eight-fold increased as compared with NC. The clinical and morphological
features, and the biochemical findings, were consistent with the diagnosis of feline
mucopolysaccharidosis VI.
Mucopolysaccharidosis VII
Rase afectate: Domestic
Fyfe JC, Kurzhals RL, Lassaline ME, Henthorn PS, Alur PR, Wang P, Wolfe JH, Giger U,
Haskins ME, Patterson DF, Sun H, Jain S, Yuhki N. 1999 Molecular basis of feline betaglucuronidase deficiency: an animal model of mucopolysaccharidosis VII.Genomics. 58(2):1218. fyfe@cvm.msu.edu A family of domestic cats was found that exhibited clinical and
biochemical abnormalities consistent with mucopolysaccharidosis VII, an autosomal recessive
lysosomal storage disorder caused by beta-glucuronidase deficiency. beta-Glucuronidase activity
was undetectable in affected cat fibroblasts and restored by retroviral gene transfer of rat betaglucuronidase cDNA. beta-Glucuronidase mRNA was normal in affected cat testis by Northern
blot analysis. Normal feline beta-glucuronidase cDNA was cloned and characterized, and
amplified from affected cat fibroblasts by reverse transcription coupled polymerase chain
reaction. There was a G-to-A transition in the affected cat cDNA that predicted an E351K
substitution, destroyed a BssSI site, and eliminated GUSB enzymatic activity in expression
studies. Multiple species comparison and the crystal structure of human beta-glucuronidase
indicated that E351 is a highly conserved residue most likely essential in maintenance of the
enzyme's conformation. BssSI digestion of polymerase chain reaction products amplified from
genomic DNA indicated that affected cats were homozygous and cats with half-normal betaglucuronidase activity were heterozygous for the missense mutation. Carriers identified in this
manner produced affected kittens in prospective breedings, and a feline MPS VII breeding
colony has been established.
Muscular dystrophy
Rase afectate: Maine Coon
Laminin alpha2 deficiency-associated muscular dystrophy Poncelet L, Resibois A, Engvall E,
Shelton GD. 2003 Laminin alpha2 deficiency-associated muscular dystrophy in a Maine coon
cat. J Small Anim Pract. 44(12):550-2. A European case of laminin alpha2 deficiency-associated
muscular dystrophy in a 12-month-old, female Maine coon pedigree cat is reported. The history
and eventual clinical presentation of this cat differed from those of two cats reported in the USA.
In this case, the myopathy was characterised by progressively worsening weakness, muscle
atrophy and joint contracture. Tendon reflexes were diminished, and motor nerve conduction
velocities were slowed. Muscle biopsy demonstrated a dystrophic phenotype with endomysial
fibrosis. Occasional thinly myelinated nerve fibres were present within a peripheral nerve
specimen. Poorly myelinated fibres were also found at the root level on necropsy specimens.
Immunohistochemical staining revealed the absence of laminin alpha2. The cat's family history
did not indicate genetic transmission of the disease.
Myocardial disease
Feline myocardial disease (cardiomyopathy) includes hypertrophic cardiomyopathy (HCM),
restrictive cardiomyopathy (RCM) and dilated cardiomyopathy (DCM). It is the most common
cardiac disorder observed in cats (Ferasin, 2009). Ferasin (2009) provides best review of feline
myocardial disease this webmaster has ever seen. Clinical signs: heart murmur (60% cases),
dyspnoea (50%), tachycardia (30%) lethargy (20%) hypotension (15%), poor body condition
(10%), ascites (10%), arrythmia (10%), collapse (10%), abnormal respiratory sounds (10%),
hindlimb paresis (7.5%), bradycardia (5.5%), muffled heart sounds (5.0%) Ferasin (2009).
Breeds: British Shorthair, Maine Coons, Norwegian Forest Cats, Ragdolls Mode of inheritance
(HCM) : autosomal dominant mode in Maine Coon and maybe also in British Shorthair and
Ragdolls (Ferasin, 2009) Reference Ferasin L. 2009 Feline myocardial disease. 1: Classification,
pathophysiology and clinical presentation. J Feline Med Surg. 11(1):3-13.
Myopathy
Rase afectate: Devon Rex, Maine Coon
Neutrophil granulation anomaly
Rase afectate: Birman
References Hirsch VM, Cunningham TA. 1984 Hereditary anomaly of neutrophil granulation in
Birman cats. Am J Vet Res. 45(10):2170-4. A hereditary anomaly of neutrophil granulation in
purebred Birman cats was described with respect to genetic, electron microscopic, histochemical,
and functional characters. The trait was inherited in an autosomal recessive manner and was
prevalent in the population studied. Affected cats had fine eosinophilic granules in the cytoplasm
of neutrophils. The granules had normal morphology as determined by electron microscopy and
did not stain for acid mucopolysaccharide. Bactericidal activity, phagocytosis, and oxidative
function of affected neutrophils were not different from those of unaffected neutrophils. The
anomaly was concluded to be an alteration in the content of lysosomal granules with increased
affinity for acidic dyes.
Niemann-Pick disease - vezi Sphingomyelinase deficiency ,
Ocular abnormalities and disease
Rase afectate: Burmese, Himalayan, Persian, Siamese
References Glaze MB. 2005 Congenital and hereditary ocular abnormalities in cats.Clin Tech
Small Anim Pract. 20(2):74-82. mglaze3937@aol.com Congenital and inherited ocular diseases
are reported less frequently in the cat than the dog. The 2 species also differ in their array of
disorders, with familiar canine abnormalities like cataracts overshadowed by unique feline
diseases such as eyelid agenesis and corneal sequestration. Organized according to the primary
ocular structure affected and commingling congenital and inherited disorders in each section, the
review begins with multiple ocular anomalies and their impact on globe-orbit relationship.
Adnexal disorders include eyelid agenesis, entropion, dermoid, and nictitans gland protrusion.
Corneal abnormalities range from the routine sequestrum and PPM-related opacity to those rare
infiltrates accompanying inborn errors of metabolism. Brief descriptions of uveal anomalies,
primary glaucoma, cataracts, and lens luxations follow. Retinal dysplasia and progressive retinal
atrophy complete the summary. Suspicions of heritability are often based on small numbers of
animals in sporadic reports of ocular disease, but the Persian, Burmese, and Siamese are among
the breeds repeatedly linked with one or more of these disorders. Narfstrom K. 1999 Hereditary
and congenital ocular disease in the cat.J Feline Med Surg. 1 (3):135-41. The aim of this review
of hereditary and congenital ocular disease in cats is to present an overview of the most common
disorders seen in this species, the pathogenesis of the problems and wherever possible, how they
are treated. Several defects are common in breeds such as the Persian, Himalayan and Burmese
cats and affect the anterior segment of the eye. Examples are agenesis of the eyelids, dermoids,
entropion and corneal sequestrum. Other problems such as cataracts, lens luxation and retinal
dysplasia, cause problems of the intraocular structures, but are less common in cats compared to
dogs. Finally, various parts of the retina and in some diseases other parts of the eye, are
specifically affected by hereditary diseases. Examples of these are lysosomal storage disease,
Chediak-Higashi syndrome and progressive rod cone degeneration and rod cone dysplasia.
Research of the latter two hereditary diseases, both described in the Abyssinian breed of cat,
have made affected individuals important animal models for research into comparable diseases
of humans.
Osteochondromatosis
Levitin B, Aroch I, Aizenberg I, Foreman O, Shamir M. 2003 Linear osteochondromatosis in a
cat.Vet Radiol Ultrasound. 2003 Nov-Dec;44(6):660-4. A domestic shorthair cat was presented
with quadriparesis and lumbar hyperesthesia that progressed over 4 months. There were linear
and amorphous radiopaque masses throughout the soft tissue surrounding the long bones,
vertebral bodies, ribs, pelvis, and scapula. The diagnosis of osteochondromatosis was confirmed
by histopathology. Unlike previously reported patients with osteochondromatosis, most of the
calcified masses in this cat were not connected to the periosteum; some were linear and were
arranged parallel to the long bones involved.
Osteodystrophy
Rase afectate: Scottish Fold
Reference Mathews KG, Koblik PD, Knoeckel MJ, Pool RR, Fyfe JC.1995 Resolution of
lameness associated with Scottish fold osteodystrophy following bilateral ostectomies and
pantarsal arthrodeses: a case report.J Am Anim Hosp Assoc. 31(4):280-8. Bilateral hind-limb
lameness, associated with tarsal exostoses in a Scottish fold diagnosed as having Scottish fold
osteodystrophy, resolved following staged bilateral ostectomies and pantarsal arthrodeses.
Degenerative changes in the phalangeal joints of the hind limbs have progressed
radiographically, but lameness has not recurred 48 weeks following the second arthrodesis.
Additional skeletal abnormalities were detected radiographically in both carpi and in several
caudal vertebrae. A partial, left-sided conduction deafness was diagnosed by evaluating brain
stem auditory-evoked responses.
Patent ductus arteriosis
Straw RC, Aronson EF, McCaw DL. 1985 Transposition of the great arteries in a cat. J Am Vet
Med Assoc. 187(6):634-6. Transposition of the great arteries, a congenital cardiac disorder, was
diagnosed in a 4-month-old domestic short-haired kitten. Angiography revealed a patent ductus
arteriosis, with the pulmonary artery originating from the left ventricle and the aorta originating
from the right ventricle. Blood gas analysis suggested a high ventricular septal defect. Necropsy
confirmed the diagnosis.
Pelger-Huet anomaly
DSH, Autosomal dominant inherited disorder. Homozygous form is lethal. Heterozygote cats
show granulocyte hypo-segmentation. Cells usually classified as immature or band neutrophils,
but appear to have normal function.
Polycystic kidney disease
Rase afectate: Persian, Exotic shorthair
Polycystic kidney disease (PKD) is an inherited condition of cats and humans. In Persians, the
condition has been shown to be inherited as a single autosomal dominant gene. It is estimated
over 37% of Persians have PKD1, a breed that accounts for nearly 80% of the cat fancy.
Diagnosis is by ultrasound. A DNA test is available from the Veterinary Genetics Laboratory
(VGL) at the University of California, Davis. All that is required is a swab of the buccal mucosa,
instructions and a submission form can be found on the VGL website. The Feline Advisory
Bureau runs a PKD negative cat register. For screening by ultrasound, cats need to be at least 10
months old, whereas screening for the PKD1 gene can be done as soon as a DNA sample can be
obtained. Gene test submission forms can be downloaded from the Feline Advisory Bureau
website. References Greco DS. 2001 Congenital and inherited renal disease of small animals.Vet
Clin North Am Small Anim Pract. 31(2):393-9, viii. dgreco@vth.colostate.edu Congenital renal
diseases are present at birth and may be determined genetically; familial renal disorders occur in
related animals with a higher frequency than would be expected by chance, and frequently are
inherited. The most common familial disorders in cats and dogs include renal amyloidosis, renal
dysplasia, polycystic kidneys, basement membrane disorders, and tubular dysfunction (Fanconi's
syndrome). This article alerts the veterinarian to commonly observed congenital and hereditary
conditions of the kidneys in small animals.
Polyneuropathy
Porphyria
Rase afectate: Siamese
Giddens WE Jr, Labbe RF, Swango LJ, Padgett GA. 1975 Feline congenital erythropoietic
porphyria associated with severe anemia and renal disease. Clinical, morphologic, and
biochemical studies.Am J Pathol. 80(3):367-86. A feline erythropoietic porphyria was studied in
an affected female Siamese cat and 2 male offspring. The principal elevated porphyrins were
Type I isomers of uroporphyrin and coproporphyrin; the porphyrin precursors, porphobilinogen
and sigma-aminolevulinic acid, were also detected. Porphyrins were present in the blood and in
all the viscera, teeth, bones, and excreta. There was severe macrocytic hypochromic anemia,
hepatomegaly, splenomegaly, and uremia associated with a renal disease characterized by
mesangial hypercellularity and proliferation (resulting in narrowing of glomerular capillaries)
and ischemic tubular injury. There was thickening of tubular basement membranes and tubular
epithelial lipidosis, degeneration, and necrosis. Electron microscopic studies of bone marrow and
kidney revealed the presence of membrane-enclosed lamellar bodies 150 to 1000 nm in diameter
in cytoplasmic and extracellular locations.
Progressive retinal atrophy (PRA)
Rase afectate: Abysinnian, Persian
Clinical signs: bilateral, leads to blindness. In Abysinnian, usually present by 3-4 years of age,
earliest report only 7 months old. In Persians, pupillary light reflexes (PLR) were reduced as
early as 16 weeks of age and diminution of the extent and speed of the PLR could be detected by
the discerning as early as 2-3 weeks of age. Mode of inheritance: autosomal recessive References
Barnett KC, Curtis R. 1985 Autosomal dominant progressive retinal atrophy in Abyssinian cats.J
Hered. 76(3):168-70. Hereditary progressive retinal atrophy in Abyssinian cats in England is
recorded. It is compared with another hereditary retinopathy in the same breed in Sweden and it
is concluded that these are two distinct conditions, one occurring at an early age in kittens with
an autosomal dominant mode of inheritance, the other occurring in young adult cats due to an
autosomal recessive gene. The two diseases are bilateral, progressive, and of the generalized
type, and are similar ophthalmoscopically. Djajadiningrat-Laanen SC, Vaessen MM, Stades FC,
Boeve MH, van de Sandt RR. 2002 Progressive retinal atrophy in Abyssinian and Somali cats in
the Netherlands (1981-2001) Tijdschr Diergeneeskd. 127(17):508-14. From 1981 to 2001, 248
Abyssinian and 127 Somali cats in the Netherlands were examined for hereditary eye disease.
Distinct ophthalmoscopic signs consistent with hereditary progressive retinal atrophy (PRA)
were observed in 11 Abyssinian cats, and subtle signs in 3 Abyssinian cats. A familial
relationship was detected in 13 out of 14 of these cats, which supports a hereditary basis to the
condition. Distinct funduscopic signs of retinal degeneration were observed at a median age of 4
years. One cat with advanced retinal degeneration was only 7 months old, whereas the remaining
10 cats were between 2 and 12 years old at the time of diagnosis. These differences in the age of
onset are suggestive of at least two types of PRA occurring in Abyssinian cats in the
Netherlands: a dysplastic, early-onset and a late-onset retinal degeneration. A large-scale and
systematic examination programme for hereditary eye disease will be necessary to assess the
incidence of PRA in the Dutch population of Abyssinian and Somali cats as a whole, and to
provide a basis for a preventive breeding programme. Narfstrom K. 1983 Hereditary progressive
retinal atrophy in the Abyssinian cat. J Hered. 74(4):273-6. Progressive retinal atrophy (PRA), a
hereditary eye disease leading to blindness, was found in the Abyssinian breed of cat. Sixty-eight
cases of a bilateral generalized retinopathy, at different stages of the disease process, were seen
in the breed during ophthalmoscopic examinations of cats throughout Sweden during a 2-year
period. Forty-five percent of cats aged 2 years or older were affected in the examined group. The
earliest case was diagnosed in a 16-month-old cat. At the age of 3-4 years a bilateral retinal
atrophy was usually present in affected cats. Genetic analysis indicates that PRA in the
Abyssinian cat is caused by an autosomal recessive gene. Narfstrom K. 1985 Progressive retinal
atrophy in the Abyssinian cat. Clinical characteristics.Invest Ophthalmol Vis Sci. 26(2):193-200.
Ninety-four cases of a hereditary retinal degeneration in household Abyssinian cats were found
in Sweden, mainly during a 3-year period. The disease was investigated by ophthalmoscopy,
fluorescein angiography, electroretinography, and light microscopy. A bilateral retinopathy was
usually first seen in affected cats at the age of 1.5-2 years. Fluorescein angiography did not
demonstrate abnormalities of etiological significance to the disease process. A reduction mainly
of a- and b-wave amplitudes in the ERG indicated a generalized photoreceptor disease. Light
microscopy showed that the photoreceptor layer was primarily affected, while other retinal layers
were mainly normal. The midperipheral and peripheral retina was affected more severely than
the retina of the posterior pole until late stages of disease, when there was a generalized loss of
photoreceptors. The clinical and laboratory findings suggest that PRA in these Abyssinian cats is
a heritable photoreceptor degenerative disease with a fairly slow rate of progression. Rah H,
Maggs DJ, Blankenship TN, Narfstrom K, Lyons LA. 2005 Early-onset, autosomal recessive,
progressive retinal atrophy in Persian cats. Invest Ophthalmol Vis Sci. 46(5):1742-7 PURPOSE:
An early-onset retinal degenerative disease has been identified in Persian cats. This study
genetically, clinically, and histologically characterized the disease. A breeding colony was
established to assist with identification of the causative gene and to provide a resource for vision
research. METHODS: Cats were produced from testcross breedings. Kittens underwent serial
ophthalmic and neuro-ophthalmic examinations. Globes were harvested from age-matched
affected, obligate carrier, and control cats and were evaluated by light microscopy. Fluorescein
angiography assessed retinal and choroidal vasculature. RESULTS: Test breedings confirmed an
autosomal recessive mode of inheritance. Rate and extent of disease progression were similar
among individual affected cats. The earliest clinical signs (reduced pupillary light reflexes) were
seen at 2 to 3 weeks of age. Retinal degeneration was virtually complete by 16 weeks of age.
Histologic changes progressed rapidly and paralleled clinical findings. Histologic lesions were
limited to the photoreceptors, outer plexiform layer, and retinal pigment epithelium in all but the
terminal stages, when subtle changes were noted within the inner nuclear layer.
CONCLUSIONS: Characterized in this study was an autosomal recessive, early-onset, retinal
degenerative disease in Persian cats that is likely to be more prevalent in this breed than
previously suspected. This feline disease model may identify a new gene or provide biological
insight into some forms of early-onset retinitis pigmentosa (RP) in humans and genetic retinal
degenerations in other species. A breeding colony that will assist in the identification of the
causative gene has been established and is available for studies in vision research. Sarva R.1986
Progressive retinal atrophy in the Abyssinian cat. Nord Vet Med. 38(6):388-93. Eight cases of
hereditary progressive retinal atrophy in Abyssinian cats in Denmark are reported. Pedigree
studies indicate direct lineage to affected cats of the same breed in Sweden. The disease is
bilateral, progressive, and of the generalized type, and ultimately leads to blindness.
Pyruvate kinase deficiency
Rase afectate: Abyssinian, DSH, Somali
Clinical signs: intermittent haemolytic anaemia, jaundice, splenomegaly Mode of inheritance:
autosomal recessive Link to testing laboratory: Josephine Deubler Genetic Testing Laboratory,
Pennsylvania, USA. Link to submission form for genetic test from the Josephine Deubler
Genetic Testing Laboratory, Pennsylvania, USA. References Mansfield CS, Clark P. 2005
Pyruvate kinase deficiency in a Somali cat in Australia. Aust Vet J. 83(8):483-5.
Renal calculi
Rase afectate: Birman, Tonkinese
Ling GV, Ruby AL, Johnson DL, Thurmond M, Franti CE. 1998 Renal calculi in dogs and cats:
prevalence, mineral type, breed, age, and gender interrelationships (1981-1993).J Vet Intern
Med. 1998 Jan-Feb;12(1):11-21. gvling@ucdavis.edu Three hundred seventeen specimens of
urinary calculi of renal origin from 214 female dogs and 103 male dogs, and 71 specimens of
urinary calculi of renal origin from 38 female cats and 33 male cats were submitted for mineral
analysis between July 1, 1981, and December 31, 1993. Among dogs, 45 breeds were affected
with renal calculi. Thirty-three breeds and a crossbred group were represented among females,
but 8 breeds and the crossbred group accounted for 81% of the total. Among male dogs, 30
breeds and a crossbred group were represented, but 7 breeds and the crossbred group accounted
for 69% of the total. Among cats, 10 breeds and a crossbred group were represented. Dogs and
cats with renal calculi were older than those of 2 comparison population groups. More than onehalf of the renal calculi in both dogs and cats were from the 1st known episode of urolithiasis.
The risk of formation of renal calculi was found to be higher for cats than for dogs, when
compared to other stone-forming cats and dogs (approximately 4.95 per 100 stone-forming cats
and 2.88 per 100 stone-forming dogs). Among dogs, breeds at highest risk of developing renal
calculi were Miniature Schnauzers, Shih Tzus, Lhasa Aposos, Yorkshire Terriers, and female
Pugs. Also at high risk were male Dalmatians and male Basset Hounds. Among small dogs,
females generally were at higher risk of developing renal calculi than were males. Regardless of
size, terrier breed males generally were at higher risk of developing renal calculi. Breeds of dogs
at low risk for development of renal calculi included crossbreds. German Shepherd Dogs,
Labrador Retrievers, Golden Retrievers, and female Dachshunds. When only 1 kidney was
involved, the risk of left renal calculus was greatest for both dogs and cats, but bilateral renal
involvement was relatively common in both species (19% and 9%, respectively). Among dogs,
specimens composed of 1 mineral substance (e.g., struvite) occurred more often in males
(58.3%) than in females (37.9%). Female dogs formed renal calculi containing struvite or oxalate
more often than did males; males formed calculi containing urate more often than did females.
Calculi containing oxalate, apatite, or some combination of these minerals predominated among
cats; only 1 specimen from 38 female cats and only 4 specimens from 33 male cats contained
neither oxalate nor apatite. Crossbred cats were significantly less likely to have renal calculi than
were other breeds. A single renal calculus specimen was identified in several uncommon breeds
including Tonkinese and Birman cats, and Affenpinscher, Clumber Spaniel, English Shepherd,
and Field Spaniel dogs. No significant differences were observed between male and female dogs
or between male and female cats with regard to mineral type of the specimen and the presence of
urinary tract infection.
Retinal atrophy - vezi Progressive retinal atrophy (PRA),
Rase afectate: Abysinnian
Clinical signs: marked dilatation of the pupils, impairment of the pupillary light reflex, and
nystagmus Mode of inheritance: autosomal dominant Curtis R, Barnett KC, Leon A. 1987 An
early-onset retinal dystrophy with dominant inheritance in the Abyssinian cat. Clinical and
pathological findings.Invest Ophthalmol Vis Sci. 28(1):131-9. The clinical and pathological
features of an early-onset autosomal dominant photoreceptor degeneration in the Abyssinian cat
are described. Ophthalmoscopic evidence of retinal disease at 8-12 weeks of age was always
preceded by marked dilatation of the pupils, impairment of the pupillary light reflex, and
nystagmus. The electroretinogram was unrecordable in all but one of the affected individuals
examined. Abnormal photoreceptor development was observed by both light and electron
microscopy in retinas of a 22-day-old kitten; in this individual, no outer segment material was
detected, and inner segments showed impaired development which was more severe towards the
posterior pole. In a 40-day-old kitten, the inner segments were relatively well-formed, whereas
the outer segments, though present, showed marked disorganization and degenerative change.
The retinas of older individuals showed more advanced photoreceptor degeneration, with
thinning of the neural retina. This early-onset retinopathy, which may be classified as a rod-cone
dysplasia, is distinct from the hereditary retinal dystrophy (progressive retinal atrophy)
previously described in this breed. The gene symbol Rdy has been adopted. Gould DJ, Sargan
DR. 2002 Autosomal dominant retinal dystrophy (Rdy) in Abyssinian cats: exclusion of PDE6G
and ROM1 and likely exclusion of Rhodopsin as candidate genes.Anim Genet. 33(6):436-40.
d.j.gould@bris.ac.uk Retinal dystrophy (Rdy) is an autosomal dominant photoreceptor dysplasia
of Abyssinian cats and a model for autosomal dominant retinitis pigmentosa (ADRP) in man. We
have pursued a candidate gene approach in the search for the causal mutation in Rdy. The genes
RHO (encoding rhodopsin), ROM1 (encoding the structural retinal outer-membrane protein-1)
and PDE6G (encoding the gamma subunit of the visual transduction protein cyclic guanosine
monophosphate-phosphodiesterase) were polymerase chain reaction-amplified from normal
feline genomic DNA. Leader, coding and 3' untranslated regions of each gene, and parts of
introns were sequenced. Single-stranded conformation polymorphism (SSCP) analysis of Rdyaffected and normal cats was used to identify intragenic polymorphisms within ROM1 and
PDE6G. DNA sequencing of all three genes in Rdy-affected cats was used to confirm results
from SSCP. For both ROM1 and PDE6G polymorphisms identified by SSCP and sequencing
showed disconcordance between the polymorphism and the disease phenotype within an Rdy
disease pedigree. SSCP analysis of RHO performed across the 5' untranslated region, the entire
coding sequence and the intron/exon boundaries in Rdy-affected and control cats failed to
identify any intragenic polymorphisms that could be used for linkage analysis. DNA sequencing
of these regions showed no differences between Rdy-affected and control cats. Mutations in
ROM1 or in PDE6G are not causative of feline Rdy. The absence of potentially pathogenic
polymorphisms in sequenced portions of the RHO gene makes it unlikely that a mutation in this
gene is the cause of Rdy.
Retinal degeneration - vezi Mucolipidosis type II,
Retinal dystrophy
Rod cone degeneration/rod cone dysplasia
Rase afectate: Abysinnian
Clinical signs: the retina is, in most cases, ophthalmoscopically normal until the age of 1.5-2
years. The retinal changes that then appear are slowly progressive and lead to a generalized
retinal atrophy in another 2-4 years. Reference Narfstrom K, Nilsson SE. 1987 Hereditary rodcone degeneration in a strain of Abyssinian cats. Prog Clin Biol Res. 247:349-68. The retinal
disease found in this strain of Abyssinian cats is a heritable disorder, primarily affecting the
photoreceptors. The retina is, in most cases, ophthalmoscopically normal until the age of 1.5-2
years. The retinal changes that then appear are slowly progressive and lead to a generalized
retinal atrophy in another 2-4 years. It is obvious that this cat retinal degeneration shows many
similarities to human Retinitis Pigmentosa. Just as in RP the midperiphery/periphery is most
severely affected at the earlier stages, and with progression of disease alterations become
generalized, the central retina being the best preserved area until the very late stage. Rods are
affected prior to cones, but later in the disease there is an involvement of both rods and cones.
Also, the disease process is slow, starting off from an ophthalmoscopically normal appearing
retina. This strain of Abyssinian cats, affected by the presently described retinal disease,
therefore has the potential of becoming a new animal model in the study of hereditary visual cell
disease processes.
Sacrocaudal dysgenesis
Rase afectate: Manx
Clinical signs: Mode of inheritance: autosomal dominant Jones BR 2004 The nervous system.
Feline Medicine and Therapeutics. Third Edition Eds (Chandler EA. Gaskell CJ & Gaskell, RM)
125-171
Sandhoff disease - vezi Gangliosidosis,
Sphingomyelinase deficiency
Clinical signs: hepatosplenomegaly, progressive neuromuscular disease Mode of inheritance:
autosomal recessive References Brown DE, Thrall MA, Walkley SU, Wurzelmann S, Wenger
DA, Allison RW, Just CA. 1996 Metabolic abnormalities in feline Niemann-Pick type C
heterozygotes. Inherit Metab Dis. 19(3):319-30. Niemann-Pick disease type C (NPC) is an
autosomal recessive neurovisceral lysosomal storage disorder in which cholesterol lipidosis
results from defective intracellular transport of unesterified cholesterol. The primary molecular
defect of NPC is unknown; regulatory mechanisms of cholesterol metabolism are impaired,
resulting in retarded esterification of exogenous cholesterol with accumulation of unesterified
cholesterol in lysosomes and secondary storage of glycolipids and sphingomyelin. In obligate
heterozygotes from a feline NPC model, cultured skin fibroblasts challenged with exogenously
derived cholesterol exhibited intermediate rates of cholesterol esterification and accumulation of
unesterified cholesterol. Liver lipid analyses of obligate heterozygote cats demonstrated
intermediate cholesterol and sphingomyelin concentrations. Vacuolated skin fibroblasts were
found in 2 of 3 heterozygote cats, and occasional cortical neurons exhibited intracellular
inclusions immunoreactive for GM2-ganglioside. Ultrastructural studies provided evidence of
storage in liver and brain. We believe these morphological and biochemical findings are the first
example of manifestations of CNS abnormalities in a genetic carrier for a neuronal storage
disease. Cuddon PA, Higgins RJ, Duncan ID, Miller SP, Parent JM, Moser AB. Polyneuropathy
in feline Niemann-Pick disease.Brain. 1989 112 ( Pt 6):1429-43. Two related cats, aged 5 months
and 7 months, and 1 unrelated cat, aged 4 months, presented with signs of a progressive
neuromuscular disease. Detailed electrophysiological studies suggested a primary demyelinating
polyneuropathy, which was confirmed by muscle and nerve biopsies and on necropsy
examination. Light and electron microscopic findings indicated a lysosomal storage disease,
which was diagnosed as sphingomyelinase deficiency (Niemann-Pick disease) by enzyme
analysis and lipid fractionation, although significant biochemical differences existed between the
2 related cats and the third cat. Several lines of evidence suggest that these 2 related cats were
affected with a variant of type A Niemann-Pick disease, whereas cat 3 represented classic
Niemann-Pick disease type A. Garver WS, Somers K, Krishnan K, Mitchell T, Heidenreich RA,
Thrall MA. 2002 The Niemann-Pick C1 protein in feline fibroblasts.Mol Genet Metab. 76(1):316. wgarver@peds.arizona.edu Niemann-Pick type C (NPC) disease is a rare inherited metabolic
disorder characterized by hepatosplenomegaly, progressive neurodegeneration, and storage of
lipids such as cholesterol and glycosphingolipids in most tissues. The current study was
conducted to characterize the Niemann-Pick C1 (NPC1) protein in feline fibroblasts. This was
accomplished by generating rabbit polyclonal antibodies against a peptide corresponding to
amino acids 1256-1275 of the feline NPC1 protein. The results obtained using immunoblot
analysis identified two major proteins that migrated at approximately 140 and 180 kDa. These
two proteins were absent when immunoblots were incubated in the presence of feline NPC1
antibody and immunizing peptide, or preimmune serum. Fluorescence microscopy of feline
fibroblasts incubated with the feline NPC1 antibody revealed granular staining within the
perinuclear region of the cell. This granular staining was diminished when feline fibroblasts were
incubated in the presence of feline NPC1 antibody and immunizing peptide, or was completely
absent when feline fibroblasts were incubated in the presence of preimmune serum. Additional
studies using double-labeled fluorescence microscopy indicated that feline NPC1 partially
colocalized with markers for late endosomes/lysosomes, endoplasmic reticulum, and
microtubules, but not the trans-Golgi network. In summary, the results presented in this report
demonstrate that the NPC1 protein in feline fibroblasts has a similar distribution as that
previously described for human and murine fibroblasts. Somers KL, Brown DE, Fulton R,
Schultheiss PC, Hamar D, Smith MO, Allison R, Connally HE, Just C, Mitchell TW, Wenger
DA, Thrall MA. 2001 Effects of dietary cholesterol restriction in a feline model of Niemann-Pick
type C disease.J Inherit Metab Dis. 24(4):427-36. A feline model of Niemann-Pick disease type
C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of
disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8
weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal
was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically
reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids.
Neurological progression of disease was not altered and dietary cholesterol restriction did not
significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had
decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol
concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and
phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated
cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated
cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a
diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a
heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected
untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages.
Although some hepatic parameters were modified, dietary cholesterol restriction did not appear
to alter disease progression in NPC-affected kittens. Somers KL, Royals MA, Carstea ED, Rafi
MA, Wenger DA, Thrall MA. 2003 Mutation analysis of feline Niemann-Pick C1 disease.Mol
Genet Metab. 79(2):99-103. klsomers@colostate.edu Niemann-Pick C (NPC) disease is an
autosomal recessive neurovisceral lysosomal storage disorder that results in defective
intracellular transport of cholesterol. The major form of human NPC (NPC1) has been mapped to
chromosome 18, the NPC1 gene (NPC1) has been sequenced and several mutations have been
identified in NPC1 patients. A feline model of NPC has been characterized and is
phenotypically, morphologically, and biochemically similar to human NPC1. Complementation
studies using cultured fibroblasts from NPC affected cats and NPC1 affected humans support
that the gene responsible for the NPC phenotype in this colony of cats is orthologous to human
NPC1. Using human-based PCR primers, initial fragments of the feline NPC cDNA were
amplified and sequenced. From these sequences, feline-specific PCR primers were generated and
designed to amplify six overlapping bands that span the entire feline NPC1 open reading frame.
A single base substitution (2864G-C) was identified in NPC1 affected cats. Obligate carriers are
heterozygous at the same allele and a PCR-based assay was developed to identify the geneotype
of all cats in the colony. The mutation results in an amino acid change from cysteine to serine
(C955S). Several of the mutations identified in people occur in the same region. Marked
similarity exists between the human and feline NPC1 cDNA sequences, and is greater than that
between the human and murine NPC1 sequences. The human cDNA sequence predicts a 1278aa
protein with a lysosomal targeting sequence, several trans-membrane domains and extensive
homology with other known mediators of cholesterol homeostasis.
Staphyloma
Reference Skorobohach BJ, Hendrix DV .Staphyloma in a cat .Vet Ophthalmol. 2003
Jun;6(2):93-7. bskorobo@utk.edu A unilateral scleral staphyloma in an 18-month-old, female
spayed Domestic Short-haired cat was treated with excision, primary closure and fascial graft.
Other ocular abnormalities noted on examination included iris coloboma, anterior cortical
cataract, focal lens equator flattening and retinal dysplasia. The staphyloma was presumed to be
congenital in origin.
Thromboembolism
Rase afectate: Abyssinian, Birman, Ragdoll
Smith SA, Tobias AH, Jacob KA, Fine DM, Grumbles PL. 2003 Arterial thromboembolism in
cats: acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in
24 cases.J Vet Intern Med. 17(1):73-83. Records of 127 cats with arterial thromboembolism
(ATE) were reviewed. Abyssinian, Birman, Ragdoll, and male cats were overrepresented.
Tachypnea (91%), hypothermia (66%), and absent limb motor function (66%) were common. Of
90 cats with diagnostics performed, underlying diseases were hyperthyroidism (12),
cardiomyopathy (dilated [8], unclassified [33], hypertrophic obstructive [5], hypertrophic [19]),
neoplasia (6), other (4), and none (3). Common abnormalities were left atrial enlargement (93%),
congestive heart failure (CHF, 44%), and arrhythmias (44%). Of cats without CHF, 89% were
tachypneic. Common biochemical abnormalities were hyperglycemia, azotemia, and abnormally
high serum concentrations of muscle enzymes. Of 87 cats treated for acute limb ATE, 39 (45%)
survived to be discharged. Significant differences were found between survivors and
nonsurvivors for temperature (P < .00001), heart rate (P = .038), serum phosphorus concentration
(P = .024), motor function (P = .008), and number of limbs affected (P = .001). No significant
difference was found between survivors and nonsurvivors when compared by age, respiratory
rate, other biochemical analytes, or concurrent CHE A logistic regression model based on rectal
temperature predicted a 50% probability of survival at 98.9 degrees F (37.2 degrees C). Median
survival time (MST) for discharged cats was 117 days. Eleven cats had ATE recurrences, and 5
cats developed limb problems. Cats with CHF (MST: 77 days) had significantly shorter survival
than cats without CHF (MST: 223 days; P = .016). No significant difference was found in
survival or recurrence rate between cats receiving high-dose aspirin (> or = 40 mg/cat q72h) and
cats receiving low-dose aspirin (5 mg/cat q72h). Adverse effects were less frequent and milder
for the lower dosage.
Type IV glycogen storage disease
Urinary tract
Kruger JM, Osborne CA, Lulich JP, Oakley RE. 1996 Inherited and congenital diseases of the
feline lower urinary tract.Vet Clin North Am Small Anim Pract. 26(2):265-79. Congenital
urinary tract disorders of young cats may result from heritable (genetic) or acquired disease
processes that affect differentiation and growth of the developing urinary tract, or from similar
disease processes that eventually affect the structure or function of the mature urinary system.
Although congenital diseases of the feline lower urinary tract are uncommon, clinical signs
associated with these anomalies may be indistinguishable from those of other acquired causes of
lower urinary tract disease. Early detection and proper management of congenital disorders may
result in restoration of urinary bladder and urethral function and/or progressive urinary tract
dysfunction.
Ventricular septal defect
Rase afectate: Domestic
Thomas WP. 2005 Echocardiographic diagnosis of congenital membranous ventricular septal
aneurysm in the dog and cat. J Am Anim Hosp Assoc. 41 (4): 215-20. Membranous ventricular
septal aneurysm was diagnosed by echocardiography in 17 dogs and three cats. The aneurysm
appeared as a thin membrane protruding into the right ventricle from the margins of a congenital
ventricular septal defect (VSD). The aneurysm was intact in nine dogs and two cats and
perforated by a small VSD in eight dogs and one cat. Other congenital heart defects were present
in seven dogs. In all animals, the aneurysm was an incidental finding observed during
echocardiographic examination, and it did not appear to directly cause any cardiac dysfunction.
Vitamin K-dependent multifactor coagulopathy - vezi Coagulopathies,
Rase afectate: Devon Rex
Clinical signs: haemorrhage, prolonged clotting times, response to Vitamin K.
References: Evans RJ. 1985 The blood and haemopoietic system. In Feline Medicine and
Therapeutics. (Ed.) Chandler EA, Hilbery ADR, Gaskell CJ. 129-130
Littlewood JD, Shaw SC, Coombes LM.Vitamin K-dependent coagulopathy in a British Devon
rex cat.J Small Anim Pract. 1995 Mar;36(3):115-8.Animal Health Trust, Newmarket, Suffolk.
Deficiencies of the vitamin K-dependent coagulation factors were identified in a Devon rex cat
which had bled after castration. Haemorrhage was controlled by plasma transfusion. Clotting
times were normalised by oral administration of vitamin K. This report confirms the existence of
this bleeding disorder in a Devon rex cat in the United Kingdom.
Maddison JE, Watson AD, Eade IG, Exner T.1990 Vitamin K-dependent multifactor
coagulopathy in Devon Rex cats. J Am Vet Med Assoc. 197(11):1495-7. Department of
Veterinary Clinical Sciences, University of Sydney, N.S.W., Australia.
A coagulopathy attributable to a deficiency of vitamin K-dependent clotting factors (II, VII, IX,
and X) was diagnosed in 3 Devon Rex cats. There was no evidence for exposure to vitaminantagonist-related rodenticides. The cats did not have evidence of hepatic disease,
gastrointestinal disease, or fat malassimilation. Oral treatment with vitamin K1 resulted in
normalization of clotting factor concentrations. However, when treatment was discontinued in 2
cats, prothrombin and activated partial thromboplastin values became prolonged again, although
the cats did not have clinical signs of a bleeding disorder.
Soute BA, Ulrich MM, Watson AD, Maddison JE, Ebberink RH, Vermeer C. 1992 Congenital
deficiency of all vitamin K-dependent blood coagulation factors due to a defective vitamin Kdependent carboxylase in Devon Rex cats.Thromb Haemost. 68(5):521-5. Department of
Biochemistry, University of Limburg, Maastricht, The Netherlands.
Two Devon Rex cats from the same litter, which had no evidence of liver disease, malabsorption
of vitamin K or chronic ingestion of coumarin derivatives, were found to have plasma
deficiencies of factors II, VII, IX and X. Oral treatment with vitamin K1 resulted in the
normalization of these coagulation factors. After taking liver biopsies it was demonstrated that
the coagulation abnormality was accompanied by a defective gamma-glutamyl-carboxylase,
which had a decreased affinity for both vitamin K hydroquinone and propeptide. This
observation prompted us to study in a well-defined in vitro system the possible allosteric
interaction between the propeptide binding site and the vitamin K hydroquinone binding site on
carboxylase. It was shown that by the binding of a propeptide-containing substrate to gammaglutamylcarboxylase the apparent KM for vitamin K hydroquinone is decreased about 20-fold.
On the basis of these in vitro data the observed defect in the Devon Rex cats can be fully
explained.
Xanthomata - vezi Lipoprotein lipase deficiency,
Hypertrophic cardiomyopathy
Rase afectate: British Shorthair, Maine Coon, Ragdolls
Clinical signs: sudden death, thickened wall of left ventricle on echocardiography. Ferasin
(2009) provides best review of HCM this author has ever seen.
Mode of inheritance: autosomal dominant mode in Maine Coon and maybe also in British
Shorthair and Ragdolls (Ferasin, 2009)
References Ferasin L. 2009 Feline myocardial disease. 1: Classification, pathophysiology and
clinical presentation. J Feline Med Surg. 11(1):3-13.
Meurs KM, Sanchez X, David RM, Bowles NE, Towbin JA, Reiser PJ, Kittleson JA, Munro MJ,
Dryburgh K, Macdonald KA, Kittleson MD. 2005 A cardiac myosin binding protein C mutation
in the Maine Coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet.
14(23):3587-93.
GM1 gangliosidosis
References Cox NR, Morrison NE, Sartin JL, Buonomo FC, Steele B, Baker HJ. 1999
Alterations in the growth hormone/insulin-like growth factor I pathways in feline GM1
gangliosidosis.Endocrinology. 140(12):5698-704.
Cats affected with feline GM1 gangliosidosis, an autosomal, recessively inherited, lysosomal
enzymopathy, have progressive neurological dysfunction, premature thymic involution, stunted
growth, and premature death. Although increased membrane GM1 gangliosides can result in
increased apoptosis of thymocytes, there is not a direct correlation between thymocyte surface
GM1 and thymic apoptosis in vivo, suggesting that other factors may be important to the
pathogenesis of thymic involution in affected cats. Because GH and insulin-like growth factor I
(IGF-I) are important hormonal peptides supporting thymic function and affecting growth
throughout the body, particularly in the prepubescent period, several components of the GH/IGFI pathway were compared in GM1 mutant and normal age-matched cats. GM1 mutant cat serum
IGF-I concentrations were reduced significantly compared with those in normal cats by 150 days
of age, and GM1 mutant cats had no peripubertal increase in serum IGF-I. Additionally, IGFbinding protein-3 was reduced, and IGF-binding protein-2 was elevated significantly in GM1
mutant cats more than 200 days of age. Liver IGF-I messenger RNA and pituitary GH messenger
RNA both were reduced significantly in GM1 mutant cats. After stimulation by exogenous
recombinant canine GH, serum IGF-I levels increased significantly in GM1 mutant cats,
indicating that GH/IGF-I signaling pathways within the liver remain intact and suggesting that
alterations are external to the liver.
De Maria R, Divari S, Bo S, Sonnio S, Lotti D, Capucchio MT, Castagnaro M. 1998 Betagalactosidase deficiency in a Korat cat: a new form of feline GM1-gangliosidosis.Acta
Neuropathol (Berl). 96(3):307-14.
A 7-month-old Korat cat was referred for a slowly progressive neurological disease. Circulating
monocytes and lymphocytes showed the presence of single or multiple empty vacuoles and
blood leukocytes enzyme assay revealed a very low beta-galactosidase activity level (4.7
nmol/mg per h) as compared to unaffected parents and relatives. Histologically, the cat,
euthanized at the owner request at 21 months of age, presented diffuse vacuolization and
enlargement of neurons throughout the brain, spinal cord and peripheral ganglia, severe
cerebellar neuronal cell loss, and moderate astrocytosis. Stored material was stained with
periodic acid-Schiff on frozen sections and with the lectins Ricinus conmmunis agglutinin-I,
concanavalin A and wheat germ agglutinin on paraffin-embedded sections. Ultrastructurally,
neuronal vacuoles were filled with concentrically whorled lamellae and small membrane-bound
vesicles. In the affected cat, beta-galactosidase activity was markedly reduced in brain (18.9%)
and liver (33.25%), while total beta-hexosaminidase activity showed a remarkable increase.
Quantitation of total gangliosides revealed a 3-fold increase in brain and 1.7-fold in liver of
affected cat. High-performance thin layer chromatography (HPTLC) detected a striking increase
of GM1-ganglioside. On densitometric analysis of HPTLC bands, the absorption of GM1ganglioside band was 98.52% of all stained bands (GD1a, GD1b, GT1b). Based on clinical
onset, morphological and histochemical features, and biochemical findings, the Korat cat GM1gangliosidosis is comparable with the human type II (juvenile) form. However, clinical
progression, survival time and level of beta-galactosidase deficiency do not completely fit with
those of human type II GM1-gangliosidosis. The disease in the Korat cat is also different from
other reported forms of feline GM1-gangliosidosis.
Steiss JE, Baker HJ, Braund KG, Cox NR, Wright JC.1997 Profile of electrodiagnostic
abnormalities in cats with GM1 gangliosidosis.Am J Vet Res. 58(7):706-9.
OBJECTIVE: To determine which electrodiagnostic tests yield abnormal findings in cats with
GM1 gangliosidosis, and to determine the approximate age of onset of electrodiagnostic
abnormalities. ANIMALS: Cats (28 to 335 days old) affected with GM1 gangliosidosis (n = 11)
and unaffected controls (n = 14). PROCEDURE: Cats were grouped by age: group 1, < or = 90
days, group 2, 91 to 200 days; and group 3, > 200 days. Electrodiagnostic tests were conducted,
including needle electromyography, motor and sensory nerve conduction velocity, spinal evoked
potentials, and brainstem auditory evoked potentials. Results for control and affected cats were
compared, using the general linear model for ANOVA and Scheffe's test for multiple
comparisons. RESULTS: Needle electromyography did not reveal abnormal spontaneous activity
in skeletal muscles of any cat; furthermore, statistical analysis did not indicate significant
difference between affected and control groups for nerve conduction velocity, confirming that
degeneration of peripheral nerve fibers is not a feature of this disease. However, spinal evoked
potentials were abnormal in group-3 cats; conduction velocity within sensory pathways in the
cranial part of the spinal cord was significantly slower in GM1-affected cats (P = 0.0002).
Brainstem auditory evoked responses also were abnormal: wave V (generated in the region of the
pons) had prolonged latency in cats of groups 2 and 3 (P = 0.0003 and 0.0001, respectively, at 90
decibels sound pressure level). In the oldest cats, latencies for earlier waves within the auditory
pathway also were prolonged; wave I (generated by the cochlear nerve) was prolonged in group3 cats (P = 0.0423). CONCLUSIONS: Motor and sensory nerve conduction velocities remained
within normal limits in GM1-affected cats. However, spinal evoked potentials indicated slowing
in conduction velocity along the cranial part of the spinal cord in group 3 cats. Brainstem
auditory evoked responses indicated prolonged latencies in cats of groups 2 and 3.
GM2 gangliosidosis
Martin DR, Krum BK, Varadarajan GS, Hathcock TL, Smith BF, Baker HJ.2004 An inversion of
25 base pairs causes feline GM2 gangliosidosis variant.Exp Neurol. 187(1):30-7.
In G(M2) gangliosidosis variant 0, a defect in the beta-subunit of lysosomal beta-Nacetylhexosaminidase (EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside and
severe neurodegeneration. Distinct feline models of G(M2) gangliosidosis variant 0 have been
described in both domestic shorthair and Korat cats. In this study, we determined that the
causative mutation of G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair
inversion at the extreme 3' end of the beta-subunit (HEXB) coding sequence, which introduces
three amino acid substitutions at the carboxyl terminus of the protein and a translational stop that
is eight amino acids premature. Cats homozygous for the 25-base-pair inversion express levels of
beta-subunit mRNA approximately 190% of normal and protein levels only 10-20% of normal.
Because the 25-base-pair inversion is similar to mutations in the terminal exon of human HEXB,
the domestic shorthair cat should serve as an appropriate model to study the molecular
pathogenesis of human G(M2) gangliosidosis variant 0 (Sandhoff disease).
Muldoon LL, Neuwelt EA, Pagel MA, Weiss DL. 1994 Characterization of the molecular defect
in a feline model for type II GM2-gangliosidosis (Sandhoff disease).Am J Pathol. 144(5):110918.
The Korat cat provides an animal model for type II GM2-gangliosidosis (Sandhoff disease) that
may be suitable for tests of gene replacement therapy with the HEXB gene encoding the beta
subunit of the beta-hexosaminidases. In the present report, we examined the brain and liver
pathology of a typical Sandhoff-affected cat. We characterized the feline HEXB complementary
DNA (cDNA) and determined the molecular defect in this feline model. cDNA libraries were
produced from one normal and one affected animal, and cDNA clones homologous to human
HEXB were sequenced. In the affected cDNA clone, the deletion of a cytosine residue at
position +39 of the putative coding region results in a frame shift and a stop codon at base +191.
This disease-related deletion was consistently detected by sequencing of cloned polymerase
chain reaction amplified reverse transcribed messenger RNA from one more normal Korat and
two additional affected animals. The defect was further demonstrated using single-strand
conformational polymorphism analysis of the polymerase chain reaction products. In addition,
alternative splicing of both normal and affected messenger RNAs was demonstrated. These
results should facilitate the use of this animal model to assess gene therapy.
Yamato O, Matsunaga S, Takata K, Uetsuka K, Satoh H, Shoda T, Baba Y, Yasoshima A, Kato
K, Takahashi K, Yamasaki M, Nakayama H, Doi K, Maede Y, Ogawa H.GM2-gangliosidosis
variant 0 (Sandhoff-like disease) in a family of Japanese domestic cats.Vet Rec. 2004 Dec
4;155(23):739-44.
Erratum in: Vet Rec. 2005 Jan 15;156(3):86.
A five-month-old, female Japanese domestic shorthair cat with proportionate dwarfism
developed neurological disorders, including ataxia, decreased postural responses and generalised
body and head tremors, at between two and five months of age. Leucocytosis due to
lymphocytosis with abnormal cytoplasmic vacuolations was observed. The concentration of
G(M2)-ganglioside in its cerebrospinal fluid was markedly higher than in normal cats, and the
activities of beta-hexosaminidases A and B in its leucocytes were markedly reduced. On the
basis of these biochemical data, the cat was diagnosed antemortem with G(M2)-gangliosidosis
variant 0 (Sandhoff-like disease). The neurological signs became more severe and the cat died at
10 months of age. Histopathologically, neurons throughout the central nervous system were
distended, and an ultrastructural study revealed membranous cytoplasmic bodies in these
distended neurons. The compound which accumulated in the brain was identified as G(M2)ganglioside, confirming G(M2)-gangliosidosis. A family study revealed that there were probable
heterozygous carriers in which the activities of leucocyte beta-hexosaminidases A and B were
less than half the normal value. The Sandhoff-like disease observed in this family of Japanese
domestic cats is the first occurrence reported in Japan.