First report of ocular dryness as linked with Maple Syrup Urine Disease (MSUD)
Subjective
 Caucasian female of 35 y.o.
 Work as a clerck – computer use for 2h00/day
 Known for MSUD
o Is a rare metabolic disorder (1/200 000)
 Habitually from consanguineous parents
 Autosomal/recessive
o Characterized by a defect in the branch-chain amino acid decarboxylase
 = inability to metobolize the branched amino acid valine, leucine
ans isoleucine
o 5 clinical forms are reported
 Life expectancy : 50 years old at the most, many children died
before 1 year old.
o Clinical picture is caused by the effects of toxic metabolites (ketoisocaproic acid) on the central nervous system.
 Progressive encephalopathy in the first weeks of life
 Problems with feeding, lethargy, somnolence, associated with
cerebral edema and coma.
 Classic sign : maple syrup strong odor to the infant’s urine
 Is lethal unless dietary intake of banched amino acids is kept low
and at a balanced level and catabolism is avoid.
 PROTEINS should be withdrawn from the diet and protein
and vitamins essential intakes are limited to controlled
supplements.
 Optimal mean age to start the treatment : 5 days after birth
o Acute treatment
 Detoxification by exchange transfusions and/or haemofiltration
with intravenous glucose and insulin
o Ocular findings related to MSUD
 Optic atrophy, grey optic papilla, nystagmus, ophtalmoplegia,
strabismus and cortical blindness.
 Early diagnosis, proper therapy and subsequent vigilant
management may reduce the risks of ocular complications
 This patient is doing relatively well considering her disease and diet restrictions.
 Medication
o Birth control pill
o Anti-allergic drug (cetrizine)
o Amino-acid supplements
 Referred to U de Montréal for severe ocular dryness
o Lasted for several months, stable over time
o Discomfort, FBS, redness, lid crusting
o Had tried several OTC tears supplements without success
o Most efficient to this date : Systane Ultra (BID to QID)
o Ocular dryness is not typically associated with MSUD
 Last exam (from OD referrent, few weeks ago) : BCVA : OD +1,50 (20/30) and
OS +1,25 (20/20) add +1,75.
 Patient wants to explore other treatmenet options for her ocular dryness
OBJECTIVE
 Entering VA : Unaided (OD 20/40, OS 20/50)
 BCVA : 20/20 monocularly and binocularly (glasses)
 Slit lamp
o Posterior blepharitis grade 1+ : turbid secretions of the meibomian glands
but no clogging.
o Conjunctival and palpebral hyperemia grade 2o Corneal staining : SPK grade 2- , lower third OU
o Negative lissamine green staining
o Narrow angles
 OCT : 19 deg N, 22 deg T OD ; 17 deg N, 19 deg T OS
 IOP : 16 mm HG (10h00 AM)
 Ocular health
o Cortical lens opacity OD (trace) SN1- / Clear lens OS
o Fundi : normal – no optic atrophy
 Additional testing
o Cotton thread test : 25 mm in 15 sec
o NiBUT : less than 2 sec OU
o OSDI score : 10,4 (normal)
o Tear ferning : grade 2 – normal
ASSESSMENT
o Moderate ocular dryness : related to lipid layer deficiency
o MGD : not clinically significant
DISCUSSION
o Ocular dryness is a pathology but not habitually related to MSUD
o However corneal deepithelialization was reported in a case
o Proteins in the tear film help to lower the surface tension and to alleviate dry spots
by removing phospholipids from the ocular surface
o Hypothesis : chronic epitheliopathy with /Without protein dysfunction can lead to
tear film unstability and can explain symptoms of FBS.
Treatment :
1) Warm compresses : 10 min /day x 2 wks and then 2-3 times/wk
2) Lid hygiene and gland expression : i –lid-n-lash (iMed pharma)
Alternative : Lid Care (Novartis) or BlepharoShampoo
3) Ocular lubricant : Refresh Ultra (Allergan) QID
Alternative : Liposic (B&L)/ TO COME : SYSTANE BALANCE (Alcon)
(developped to target MGD patients)
4) Omega 3s : limited options- fish oil caps does not contain proteins but the
external enveloppe (capsule) can. Same thing for other supplements as flaxseed
oil. A consultation with a nutritionist is explored because, even if omega 3s can
help a lot patients with ocular dryness and blepharitis, there is severe limitations
in that case to use them as for other patients.
5) Consultation with a metabolic disease specialist to see if her supplementation is
adquate and balanced – to alleviate any protein dysfunction within the tear film
Patient was seen in follow-up for several weeks and remained compliant on every
phase of this treatment. Condition improved and symptoms are less present
nowadays.
CONCLUSION
Most of the rare metabolic diseases can trigger ocular side-effects. MSUD is not
frequently seen in a regular practice. This is the first time that ocular dryness is reported
as a symptom of an affected patient. It is not certain that ocular dryness can be linked to
the development of the disease but chronic corneal epitheliopathy and a possible protein
dysbalance can lead to tear film dysfunction.
Ocular dryness should be considered an ocular pathology and treated accordingly.
Patient’s education about chronicity, causes and outcomes is mandatory. Compliance on
a long term is certainly an issue, more with patients affected by chronic systemic diseases
that impact already their quality of life.
REFERENCES
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le Roux C, Murphy E, Lilburn M, Lee PJ. The longest-surviving patient with classical
maple syrup urine disease. J Inherit Metab Dis. 2006 Feb;29(1):190-4.
Burke JP, O'Keefe M, Bowell R, Naughten ER.Ophthalmic findings in maple syrup urine
disease. Metab Pediatr Syst Ophthalmol. 1991;14(1):12-5.
Gupta B, Waggoner D. Ophthalmoplegia in maple syrup urine disease. J AAPOS. 2003
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