Amino acid disorders
Triptofan
BH4
Triptofan
dihidroksilaz
C vit(+)
Tiroksin
5-hidroksi-
Melanin
triptofan (5-HT)
ALBİNİZM
TETRAHİDROBİOPTERİN
YETERSİZLİĞİ
B6 vit(+)
Melanositik tirozin
hidroksilaz
Tetrahidrobiyopterin (BH4)
Serotonin
Tirozin hidroksilaz + BH4, folik asit, niasin, demir)
Dihidroksifenilalanin (DOPA)
TİROZİN
FENİLALANİN
B6 vit(+)
Fenilalanin hidroksilaz
FENİLKETONÜRİ
TİROZİNEMİ TİP II
Dopamin
Tirozin aminotrasferaz C vit(+)
4-OH-fenilpirüvik asit
Fenilpirüvat
4-OH fenilpirüvik asit
dioksijenaz
Norepinefrin
Homovalinik
asit
TİROZİNEMİ TİP III
HAWKİNSİNÜRİ
YENİDOĞANIN GEÇİCİ
HİPERTİROZİNEMİSİ
Epinefrin
NTBC (-)
C vit(+)
Parahidroksifenilasetat
Fenillaktat
Homogentisik asit
Homogentisik
Fenilasetat
asit oksidaz
ALKAPTONÜRİ
Delta-aminoLevülinik asit
(d-ALA)
Fenilasetilglütamin
Malleoloasitik asit
İzomeraz
Süksinilaseton
Fümarilasetoasetik asit
Fümarilasetoasetat
hidrolaz
d-ALA Dehidraz
Porfobilinojen
TİROZİNEMİ TİP I
Metionin
Fümarik asit + asetoasetik asit
Adenozilmetionin
Metionin
adenoziltransferaz
Phenylketonuria (PKU)
• Enzyme defect: phenylalanine
hydroxylase (12th chromosome): more
than 400 mutations
• Incidence: Average 1:10,000 (Highest
incidence in Turkey, 1: 4,000)
Phenylketonuria (PKU): Variants
1. Classical phenylketonuria (complete or near complete enzyme
deficiency): phenylalanine levels above 20 mg/dL (<1200
mmol/L) require diet therapy
2. Atypical phenylketonuria (partial enzyme deficiency): (enzyme
activity %1-5) require partial diet therapy
3. Benign phenylketonuria. phenylalanine levels below: 10 mg/dL
(<600 mmol/L) no clinical findings, not requiring diet therapy
3. Malign phenylketonuria: Tetrahydrobiopterin (BH4=cofactor of
phenylalanine hydroxylase): Severe neurologic findings, does
not respond diet therapy. Dopamine and setotonin may be
helpful.
Phenylketonuria (PKU): Clinical
findings
• Severe brain
damage, progressive
motor-mental
retardation
• Spasticity
• Self-mutilation
• Light colored skin
and eye (yellow hair,
blue eyes; tyrosine
deficiency)
• Paralysis
• Convulsions
• Mouse-like odor in
urine and sweat.
Phenylketonuria: Diagnosis
• High phenylalanine (N: <2mg/dL) and low
tyrosine (N: <2mg/dL) levels,
• Ferric chloride test gives green color in
urine (not reliable).
• Neonatal screening: Guthrie-card (taken
between 3rd and 7th days of life)
Phenylketonuria:Therapy
• Phenylalanine restricted diet, supplementation of
tyrosine, essential amino acids and trace elements.
Goals of the therapy:
• 0-10 years: phenylalanine values: 0.7-4 mg/dL
• 11-16 years: phenylalanine values: <15 mg/dL
• 16+ years: phenylalanine values: <20 mg/dL
• Pregnant mothers with PKU: phenylalanine values <
7mg/dL
Prognosis: with immediate and efficient treatment,
normal development and intelligence
Maternal PKU= phenylketonuric
fetopathy
• Normal phenylalanine levels
• Microcephaly
• Cardiac defects
• Motor-mental retardation
• No therapy
Triptofan
BH4
Triptofan
dihidroksilaz
C vit(+)
Tiroksin
5-hidroksi-
Melanin
triptofan (5-HT)
ALBİNİZM
TETRAHİDROBİOPTERİN
YETERSİZLİĞİ
B6 vit(+)
Melanositik tirozin
hidroksilaz
Tetrahidrobiyopterin (BH4)
Serotonin
Tirozin hidroksilaz + BH4, folik asit, niasin, demir)
Dihidroksifenilalanin (DOPA)
TİROZİN
FENİLALANİN
B6 vit(+)
Fenilalanin hidroksilaz
FENİLKETONÜRİ
TİROZİNEMİ TİP II
Dopamin
Tirozin aminotrasferaz C vit(+)
4-OH-fenilpirüvik asit
Fenilpirüvat
4-OH fenilpirüvik asit
dioksijenaz
Norepinefrin
Homovalinik
asit
TİROZİNEMİ TİP III
HAWKİNSİNÜRİ
YENİDOĞANIN GEÇİCİ
HİPERTİROZİNEMİSİ
Epinefrin
NTBC (-)
C vit(+)
Parahidroksifenilasetat
Fenillaktat
Homogentisik asit
Homogentisik
Fenilasetat
asit oksidaz
ALKAPTONÜRİ
Delta-aminoLevülinik asit
(d-ALA)
Fenilasetilglütamin
Malleoloasitik asit
İzomeraz
Süksinilaseton
Fümarilasetoasetik asit
Fümarilasetoasetat
hidrolaz
d-ALA Dehidraz
Porfobilinojen
TİROZİNEMİ TİP I
Metionin
Fümarik asit + asetoasetik asit
Adenozilmetionin
Metionin
adenoziltransferaz
Tyrosinemia Type I
Enzyme defect: Fumarylacetoacetate hydroxylase
Clinical findings
• Acute infantile form: Severe liver failure, vomiting,
bleeds, sepsis, hypoglycemia, renal tubulopathy
(Fanconi syndrome)
• Chronic form: Hepatomegaly, cirrhosis, growth
retardation, rickets, hematoma, tubulopathy,
neuropathy, and abdominal pain (due to porphyrines)
Tyrosinemia Type I: Diagnosis
• High succinylacetone levels (diagnostic).
tyrosine levels: normal or slightly elevated.
• Methionine: high
• Delta-aminolevulinic acid: high (colic)
• Alfa-feto protein: very high (marker of
hepatocellular carcinoma)
Tyrosinemia Type I: Therapy
• NTBC 1 mg/kg: blocks the accumulation
of toxic metabolites (succinylacetone);
beware tyrosine elevation and give
tyrosine-restricted diet
• If this therapy fails consider liver
transplantation.
Tyrosinemia Type I: Complications
• Renal failure
• Hepatocellular carcinoma (monitor alfafeto protein), check periodically liver
ultrasongraphy and biopsy.
Prognosis: Relatively good under NTBC
treatment.
Triptofan
BH4
Triptofan
dihidroksilaz
C vit(+)
Tiroksin
5-hidroksi-
Melanin
triptofan (5-HT)
ALBİNİZM
TETRAHİDROBİOPTERİN
YETERSİZLİĞİ
B6 vit(+)
Melanositik tirozin
hidroksilaz
Tetrahidrobiyopterin (BH4)
Serotonin
Tirozin hidroksilaz + BH4, folik asit, niasin, demir)
Dihidroksifenilalanin (DOPA)
TİROZİN
FENİLALANİN
B6 vit(+)
Fenilalanin hidroksilaz
FENİLKETONÜRİ
TİROZİNEMİ TİP II
Dopamin
Tirozin aminotrasferaz C vit(+)
4-OH-fenilpirüvik asit
Fenilpirüvat
4-OH fenilpirüvik asit
dioksijenaz
Norepinefrin
Homovalinik
asit
TİROZİNEMİ TİP III
HAWKİNSİNÜRİ
YENİDOĞANIN GEÇİCİ
HİPERTİROZİNEMİSİ
Epinefrin
NTBC (-)
C vit(+)
Parahidroksifenilasetat
Fenillaktat
Homogentisik asit
Homogentisik
Fenilasetat
asit oksidaz
ALKAPTONÜRİ
Delta-aminoLevülinik asit
(d-ALA)
Fenilasetilglütamin
Malleoloasitik asit
İzomeraz
Süksinilaseton
Fümarilasetoasetik asit
Fümarilasetoasetat
hidrolaz
d-ALA Dehidraz
Porfobilinojen
TİROZİNEMİ TİP I
Metionin
Fümarik asit + asetoasetik asit
Adenozilmetionin
Metionin
adenoziltransferaz
Tyrosinemia Type II
• Enzyme defect: Cytosolic tyrosine
aminotransferase
• Clinical findings: Painful corneal lesions
(lacrimation, photophobia, scars), mild mental
retardation
• Diagnosis: High tyrosine and phenylalanine
levels
• Therapy: Tyrosine and phenylalaninerestricted diet
Triptofan
BH4
Triptofan
dihidroksilaz
C vit(+)
Tiroksin
5-hidroksi-
Melanin
triptofan (5-HT)
ALBİNİZM
TETRAHİDROBİOPTERİN
YETERSİZLİĞİ
B6 vit(+)
Melanositik tirozin
hidroksilaz
Tetrahidrobiyopterin (BH 4)
Serotonin
Tirozin hidroksilaz + BH4, folik asit, niasin, demir)
Dihidroksifenilalanin (DOPA)
TİROZİN
FENİLALANİN
B6 vit(+)
Fenilalanin hidroksilaz
FENİLKETONÜRİ
TİROZİNEMİ TİP II
Dopamin
Tirozin aminotrasferaz
C vit(+)
4-OH-fenilpirüvik asit
Fenilpirüvat
4-OH fenilpirüvik asit
dioksijenaz
Norepinefrin
Homovalinik
asit
TİROZİNEMİ TİP III
HAWKİNSİNÜRİ
YENİDOĞANIN GEÇİCİ
HİPERTİROZİNEMİSİ
Epinefrin
NTBC (-)
C vit(+)
Parahidroksifenilasetat
Fenillaktat
Homogentisik asit
Homogentisik
Fenilasetat
asit oksidaz
ALKAPTONÜRİ
Delta-aminoLevülinik asit
(d-ALA)
Fenilasetilglütamin
Malleoloasitik asit
İzomeraz
Fümarilasetoasetik asit
Fümarilasetoasetat
hidrolaz
d-ALA Dehidraz
Süksinilaseton
Porfobilinojen
TİROZİNEMİ TİP I
Metionin
Fümarik asit + asetoasetik asit
Adenozilmetionin
Metionin
adenoziltransferaz
Alcaptonuria
• Enzyme defect: Homogentisate
oxygenase
• Clinical findings: black discoloration in
urine at acid pH; mild arthritis in adults
• Diagnosis: High homogentisic acid levels in
urine
• Therapy: Protein-restricted diet? NTBC?
• Prognosis: Relatively good without
treatment
Methionine metabolism
CLASSICAL
HOMOCYSTINURIA
• Enzyme defect: Cystationine-ßsynthase
• Mechanism: Accumulation of
homocysteine (collagen disorder)
• Clinical findings: Progressive
disease, usually starting with
school age. Marfan-like appearance
(archnodactyly), progressive
myopia (the earliest finding), lens
dislocation, epilepsy, mental
retardation, osteoporosis,
thromboembolism !!!
Marfan
syndrom
HOMOCYSTINURIA
• Diagnosis: High methionine, high
homocysteine (N: 0-3.5 µmol/L) and low
cysteine levels. Positive nitroprusside test in
fresh urine
• Therapy: Pyridoxine (Vit. B6): 50-1000
mg/day + folic acid 10 mg/day.
• If this fails diet + betaine (100 mg/kg) up to
3X3 g
• Goal: Keep homocysteine <30µmol/L.
MILD HYPERHOMOCYSTEINEMIA
Causes
• Methylene tetrahydrofolate reductase
(MTHFR) polymorphism, thermolabile variant,
homozygosity, up to 5% in Europeans, 60% in
Asiasns
• Heterozygosity for cystationine-ß-synthase
• Endogenous and exogenous disorders of folic
acid metabolism
• Vitamin B12 deficiency
MILD HYPERHOMOCYSTEINEMIA
Clinical findings:
• Premature vascular disease in the 3rd and
4th decade (infarctions, thrombosis embolies)
Maternal hyperhomocysteinemia: congenital
defects
• Neural tube defects
• Cardiac output defects
• Renal defects
• Pyloric stenosis?
LÖSİN
İZOLÖSİN
VALİN
Alfa-ketoizokaproat
Alfa-keto-beta-metilvalerat
Alfa-ketoizovalerat
OKSİDATİF DEKARBOKSİLASYON: Dallı-zincirli alfa-ketoasit dehidrogenazları (B1 vit.)
AKÇAAĞAÇ ŞURUBU KOKULU İDRAR HASTALIĞI
İzovaleril CoA
İzobütiril CoA
Metilbütiril CoA
DEHİDROJENASYON: CoA dehidrogenazlar
İZOVALERİK ASİDEMİ
3-Metilkrotonil CoA
Tiglil CoA
Metakrilil CoA
ASETOASETİL CoA
İntestinal propionik asit
(bakteriler)
PROPİONİL CoA
Propionil CoA karboksilaz
PROPİONİK ASİDEMİ
Biyotin
Metilmalonil CoA
Metilmalonil CoA mütaz
B12 vit
Süksinil CoA
METİLMALONİK
ASİDEMİ
Maple syrup urine disease
Enzyme: Branched-chain alfa-ketoacid dehydrogenase
complex
Incidence: 1:200,000, autosomal recessive
Clinical findings
• Severe form: Progressive encephalopathy, cerebral
edema, lethargy, coma after the 3rd day of life,
“çemen” odor in urine and sweat
• Mild form: Developmental retardation, recurrent
ketoacidotic decompensation
Diagnosis:
• “Çemen” odor in urine and sweat, positive DNPH test
in urine (non-spesific),
• Aminoacid analysis: high valine, leucine, isoleucine and
alloisoleucine (diagnostic) levels.
Therapy:
• Acute: Detoxification (dialysis, exchange transfusion)
Augmentation of anabolism : Glucose + insulin
• Chronic: Diet (monitor leucine level) ± vitamin B1
(thiamin): 5 mg/kg/day
Disorders of amino acid
transport
Methionine Malabsorption
• Methionine malabsorption in renal tubules and
intestines.
• Clinical findings: White hair, convulsions,, diarrhea,
edema , mental retardation, odor (like beer).
• Therapy: Diet deficient in methionine.
HARTNUP DISEASE
• Defect: Intestinal and renal tubular reabsorption
defect of the neutral amino acids (alanine, valine,
threonine, leucine, isoleucine, phenylalanine, tyrosine,
tryptophan, histidine, glycine; tryptophan deficiency
leads nicotinic acid and serotonine deficiency.
• Clinical finding: Photodermatitis, cerebellar ataxia;
often asymptomatic
• Diagnosis: High levels of neutral amino acids in urine
low levels of neutral amino acids in plasma.
• Therapy: Nicotinamide 40-300 mg/day, sun
protection
LYSINURIC PROTEIN
INTOLERANCE
• Defect: Intestinal and renal tubular reabsorption
defect of the dibasic amino acids (lysine, arginine and
ornithine) lead blockage of urea cycle; lysine
deficiency
• Clinical findings: Intestinal protein intolerance,
failure to thrive, osteoporosis, and hyperammonemia
with progressive encephalopathy
• Diagnosis: Hyperammonemia, low lysine, arginine and
ornithine in plasma, high LDH levels.
• Therapy: Citrulline substitution, protein restriction
CYSTINURIA
• Defect: Renal tubular reabsorption defect of the dibasic amino
acids (lysine, arginine, ornithine and cystine)
• Clinical findings: Neprolithiasis (cystine crystallizes above 1250
µmol/L at pH 7.5)
• Diagnosis: Positive nitroprusside test in urine, increased levels of
acids lysine, arginine, ornithine and cystine in urine, plasma levels
are generally normal.
• Therapy: High (>5L) fluid intake, alkalisation of the urine (urinary
infections!). Consider penisillamine (1-2 g/day),
mercaptopropionylglycine or captopril in selected cases.
ORGANIC ACIDEMIAS
Pahogenesis
• Mitochondrial accumulation of related CoAmetabolites
Clinical findings
Acute neonatal form
•
Lethargy
•
Feeding problems
•
Myoclonic jerks
•
Dehydration
* Coma
* Hypotonia/hypertonia
* Cerebral edema
* Unusual odor
ORGANIC ACIDEMIAS: Forms
Acute intermittent form
• Recurrent episodes of acidotic coma
• Ataxia
• Focal neurologic signs
Chronic progressive form
• Failure to thrive, Anorexia
• Chronic vomiting
• Hypotonia
• Developmental retardation
ORGANIC ACIDEMIAS
Laboratory findings
•
Acidosis (increased anion gap)
•
Hyperammonemia
•
Hyperlactatemia
Diagnosis
•
Organic acids in urine (GC-MS)
•
Enzyme and DNA studies
ORGANIC ACIDEMIAS:Therapy
Acute
• Remove toxins: dialysis, hemofiltration and exchange
transfusion
• Interrupt catabolic state
• Stop protein intake
• Give carnitine (100-300 mg/kg)
Long term
• Protein restricted diet (special formulas if available)
• Carnitine
• Vitamins (Vit. B12, Vit. B1, Vit. B2, biotin)
Features of some organic acidemias
Izovaleric acidemia
Ketoacidosis, dehydration, neutropenia,
thromboscytopenia, hyperammonemia, sweety feet odor
Propionic acidemia
Motor-mental retardation, ketoacidosis, dehydration,
neutropenia, thromboscytopenia, hyperammonemia,
hipoglycemia
Methylmalonic acidemia
Motor-mental retardation, ketoacidosis, neutropenia,
thromboscytopenia, hyperammonemia, hypoglycemia,
response to vit B12 (+)
Biotinidase deficiency
Biotin (complex)
Biotinidase
Biotin (free)
piruvate
carboxylase
propionyl
CoA
carboxylase
betamethylcrotonyl
CoA
carboxylase
asetyl CoA
carboxylase
Biotinidase deficiency
Incidense
World. 1:60,000
Turkey: 1:10,000
Clinical and laboratory findings
• Severe metabolic acidosis
• Alopecia
• Seborrheic skin eruptions
• Refractory convulsions
Therapy 5-10 mg/day biotin (life long).
Urea cycle
defects
PROTEİN
Fenilbütirat
Fenilasetat
Aminoasitler
Fenilasetilglütamin
Glütamin
Alanin
Aspartat
Benzoat
İdrar
Hipürat
Glisin
Glütamat
Aminoglikozidler (-)
N-ASETİL GLÜTAMAT
SENTAZ YETERSİZLİĞİ
İntestinal bakteriler
İdrar
AMONYAK
Carbaglu (+)
(+)
N-Asetil
glütamat
Karbon dioksit
KARBAMOİL FOSFAT
SENTAZ YETERSİZLİĞİ
Orotik asit
Karbamoil fosfat
ORNİTİN TRANSKARBAMİLAZ
YETERSİZLİĞİ
mitokondri
İdrar
Orotidin
Sitrüllin
Ornitin
sitozol
ARJİNİNOSÜKSİNAT
YETERSİZLİĞİ
Arjinino süksinat
Ornitin
Ornitin 5aminotransferaz
RETİNANIN
GİRAT
ATROFİSİ
Sitrüllin
ARJİNAZ
YETERSİZLİĞİ
ARJİNİNOSÜKSİNAT
LİAZ YETERSİZLİĞİ
Arjinin
Glütamat
ÜRE
İdrar
Aspartat
TCA
Döngüsü
Fumarat
Urea cycle defects
Incidence: 1:10,000 (cumulative)
Genetics
•
Ornitine transcarbabamylase deficiency (most common urea cycle
defect, X-linked)
•
Argininosuccinate synthase deficiency (citrullinemia, (the second most
common urea cycle defect, OR)
•
Carbamylphosphate synthase I deficiency (OR)
•
Argininosuccinate lyase deficiency (argininosuccinic aciduria, OR)
•
Arginase deficiency (argininemia, OR)
Urea cycle defects:
Clinical findings
Main symptom (acute/or chronic encephalopathy) is related to high protein intake,
increased catabolism, infections or stress
Neonates:
* Poor feeding
* Lethargy
* Loss of reflexes
* Seizures
* Temperature lability
* Hyperventilation (respiratory alkalosis)
* Intracranial hemorrhages
* Progressive encephalopathy
Infants and children
* Failure to thrive
* Feeding problems
* Nausea, vomiting
* Episodic encephalopathy
* Ataxia
* Convulsions
Adolescents and adults
* Chronic neurologic symptoms
* Chronic psychiatric symptoms
* Episodic encephalopathy
* Behavioral problems
Urea cycle defects
Laboratory findings
• Hyperammonemia (generally >400 µmol/L in urea cycle
defects)
• Amino acids in serum
• Organic acids in urine
Differential diagnosis
• Organic acidurias:
• Liver diseases: neonatal hepatitis, galactosemia,
tyrosinemia, respiratory chain defects
• Transient hyperammonemia of newborn due to patent
ductus venosus.
CPS= Karbamoil fosfat sentaz OTC= Ornitin transkarbomoilaz
ASA=Arjininosüksinik asit AS=Arjininosüksinat sentaz
AL=Arjininosüksinat liaz(sitrüllinemi)
Urea cycle defects: Acute therapy
• Stop protein intake
• Interrupt catabolic state by high calorie infusion (carbohydrate
+ lipid)
• Remove ammonia when >400 µmol/L by hemodiafiltration,
hemofiltration, or hemodialysis, (periton dialysis is not effective)
• Give arginine 350 mg/kg in order to support urea cycle.
• Give sodium benzoate: 350mg/kg/day
• Give sodium phenylbutyrate 250mg/kg/day
• Aim for an ammonia concentration < 200µmol/L
Urea cycle defects
Chronic therapy
• Restriction of protein intake (1.0-1.5
g/kg/day) +arginine +
• sodium benzoate + sodium –phenylbutyrate
Prognosis
• Poor if there is prolonged coma (>3 days), and
symptoms and signs of increased intracranial
pressure
Defects of Fatty
acid oxidation
Fatty acid oxidation
Fatty acid (plasma)
Carnitine
Carnitine
enzymes
Fatty acid (mitochondria)
Beta-oxidation
(acyl CoA
dehydrogenases)
Krebs cycle
Asetil
CoA
3-ketothiolase
(tioforase)
Keton bodies
HMG CoA- liase
HMG CoAsynthase
131 ATP
Fatty acid oxidation
Ya€ as idi
Açil-CoA
Karnitin transport sistemi
Açil-CoA
FAD
FADH
VLCAD
LCAD
MCAD
SCAD
Enoil-CoA
LC-Hidrataz
Krotanaz
ß-oksidasyon
3-OH-açil-CoA
NAD
LCHAD
NADH
Laktik asit
SCHAD
NAD
3-keto-açil-CoA
LC-Tiolaz
SC-Tiolaz
NADH
Pirüvik asit
Asetil-CoA
HMG-sentaz
HMG-liaz
Krebs döngüsü
Asetoasetat
NADH
Elektron transport (solunum)zinciri
NAD
ATP
ß-OH bütirat
Glükoz
• Disorders of fatty acid oxidation
• During prolonged fasting mitochonrial
oxidation of fatty acids provides up to
80% of the total energy requirement.
Fatty acid oxidation: Etiology
Carnitine transporter deficiency
Defects of carnitine cycle
• Carnitine palmitoyltransferase I (CPTI) deficiency
• Carnitine translocase deficiency
• Carnitine palmitoyltransferase II (CPTII) deficiency
ß-oxidation defects
• Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
• Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
• Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
• Long-chain hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency
• Medium-chain hydroxyacyl-CoA dehydrogenase (LCHAD)
deficiency
• Short-chain hydroxyacyl-CoA dehydrogenase (LCHAD)
deficiency
Fatty acid oxidation:
Pathogenesis
• Insufficient energy production during
fasting
• Deficiency of mitochondrial free CoA
due to accumulation of toxic
intermediary products
Clinical findings
(Reyelike syndrome)
• Life-threatening hypoketotic
hypoglycemic coma during catabolic
states (prolonged fasting, infections,
operations)
• Liver failure
• Skeletal myopathy, cardiomyopathy
Fatty acid oxidation:
Laboratory findings
• Ketones: low, ammonia: high, glucose: low to normal,
liver enzymes: high
• Total carnitine: low (high in CPTI deficiency)
• Acyl carnitine/total carnitine: Low
• Dicarboxilic acids in urine (GS-MS)
• Acylcarnitine profile (Diagnostic)
• Enzyme studies (Fibroblasts, lymphocytes)
Fatty acid oxidation: therapy
Acute therapy
• High dose glucose (7-10 mg/kg/min), no
lipids (!)
• Carnitine (100mg/kg): not in carnitine
cylce defects, and in LCHAD deficiency
Chronic therapy
• Avoid prolonged fasting, careful
monitoring during catabolic states