Maple Syrup Urine Disorder (MSUD)
UPCM Class 2011 Block 9b
Tampo, Tanyu, Tiongson, Torio
This is a case of A.M., a 1 month-old baby boy from Bataan, admitted for the first time in PGH last August 16, 2009
With a chief complaint of poor suck
CLINICAL HISTORY
Birth and Maternal History
• Born full term to a 24 yo G2P1 (1001) mother, • via NSVD at a local hospital in Bataan• Was said to have good activity and good cry• Claimed to have 3 PNCU at a health center• Denied comorbid conditions except UTI-8mos– Treated with Cefalexin x 7 days
• Only 1 UTZ done, result was unrecalled
History of Present Illness
• Apparently well until 1st week of life• Noted to have no eye opening and was said to
have stiffening of the upper and lower ex• Consult at local hospital admitted x 7 days• Septic work-up was done, treated and
discharged with a diagnosis of neonatal sepsis
• Patient was well until 1 week PTA• Noted to have decreased milk intake with
poor sucking reflex and an episode of apparent apnea
• Consult done and noted bulging fontanelle, admitted at a different hospital for 7 days
• Antibiotics (amikacin, gentamycin) was given
• Cranial CT was done revealing a demyelinating disorder
• Lumbar tap done, results unrecalled.• Was referred to PGH
Family History
• (+) DM: maternal side, grandmother• (-) HPN, (-)BA, (-)PTB, (-) goiter, (-) cancer• (-) heart, liver, lung diseases• (-) similar conditions in the family
Immunization / Nutritional
• No vaccines received yet• Purely breastfed while the baby is well
Summary
PHYSICAL EXAMINATION
Sytemic PE• Normocephalic, open ant/posterior fontanelle, no bulging
fontanelle• Warm skin, slightly pale, (-) rashes, CRT <2secs, good turgor• Non bulging eyes, still unable to open eyes, slightly swelled
lids• (-) ear discharge, supple neck• ECE, (-) retractions, CBS]• AP, RR, (-) murmur• Globular, NABS, soft, (-) organomegaly, liver edge palpable
1 fingerbreadth below costal margin• (-) phimosis, descended testis (bilateral)• Grossly normal extremities
Neurologic Exam
• Asleep, cries to painful stimuli but no eye opening
• (-) neck rigidity, (+) babinski• CN: no facial assymetry• Motor: moves all extremity spontaneously• Sensory: withdraws to pain• DTR: 2+ uppers and lowers• Reflex: (+) grasp, moro, rooting
COURSE IN THE HOSPITAL
Day 1 (8/16/09)• Patient was admitted at Pedia ER on August 16, 2009• S/O>
– 2.4 kg, febrile, (+) sweet odor of urine, – (+) 2 ketones in urine
• A> – neonatal sepsis, hospital acquired – t/c inborn error of metabolism (MSUD)
• P>– NPO, IVF (FM) 240cc/hr, O2 support done– Dx:
• CBC, BT, electrolytes, Blood CS, CXR PAL, UA with ketones– Tx:
• meropenem (120) 96 mg IV q8• Amikacin (15) 40 mg IV OD
Day 2 (8/17/09)• Seen by Neuro due to seizures
– A> • Hospital acquired sepsis• t/c IEM (MSUD)
– P>• Continue meds• IVF
– 1) D12.5IMB– 2) start intralipid 20% solution (2g/kg/day)
• Seen by Genetics– Leucine level 4300, facilitate PD
• Referrals– Pedia Surg: for Catheter insertion for PD– Renal: for Catheter insertion
Day 2 (8/17/09)
• Admitted at Ward 9 Bed 9• TFI 175 [1] D12.5IMB (FM) , [2] intralipid (1)
• For FFP transfusion – Plt 14.8– PT 12.2 / 22.0 / 0.40 / 2.10– PTT 34.6 / 72.3
• t/s vitamin K
Day 3 (8/18/09)
• s/p Tenckhoff Catheter insertion, Right EJ cutdown
• Tx: meropenem, amikacin, vit K• IVF: D12.5IMB, intralipid via face mask
• O2 support via via face mask
PROBLEM LIST
Fluids
• S/O> patient on OGT, probable acute phase of MSUD
• A> maintain appropriate hydration and caloric intake
• P> continue IVF • 1] D12.5IMB
• 2] intralipid
Others
• S/O> still unable to spontaneously open eyes, slight swelling or upper lids, (-) discharge, (-) redness
• A> swollen lids• P> referral to Ophthalmology
Respiratory
• S/O> s/p catheter insertion• A> supportive oxygen administration• P> – continue O2 support via face mask
– To watch out for respiratory distress
Infection
• S/O> blood culture (+) Enterobacter• A> Hospital Acquired sepsis• P> continue meds– Meropenem– Amikacin
Cardiac
• S/O> AP, regular rhythm, HR 102, (-) murmurs• A> no cardiac disorder at the moment• P> none for now
Hematologic
• S/O> – Plt 14.8– PT 12.2 / 22.0 / 0.40 / 2.10– PTT 34.6 / 72.3
• A> thrombocytopenia• P> – Continue vit K– Repeat CBC, PT/PTT
Metabolic
• S/O> (+) sweet urine odor, (+) urine ketones• A> t/c MSUD• P> continue PD
Neurologic
• S/O> (+) episodes of seizure-like activity• A> seizure prob 2 to MSUD,or hypoglycemia• P> – standby diazepam at bedside– Monitor Hgt
Developmental
• S/O> (+) MSUD• A> mental and neurologic deficits are
common sequelae• P> – regular follow-up at a Pediatric clinic – Watch out for infection
MAPLE SYRUP URINE DISEASE
Branched Chain Amino Acids
Isoleucine Valine Leucine
Catabolism
• Transamination• Oxidative Decarboxylation*• Dehydrogenation• End products
* Enzyme responsible: Branched-chain α-ketoacid dehydrogenase
Branched-chain α-ketoacid dehydrogenase
• A complex enzyme system using tyrosine pyrophosphate (Vit B1) as coenzyme
• A mitochondrial enzyme consisting of four subunits E1α, E1β, E2, E3
• Deficiency of this ensyme causes Maple Syrup Urine Disease (MSUD)
MSUD
• Named after sweet odor of maple syrup found in body fluids, esp. urine
• 5 phenotypes have been identified based on clinical findings and response to thiamine– 1. Classic MSUD– 2. Intermittent MSUD– 3. Mild (Intermediate) MSUD– 4. Thiamine-responsive MSUD– 5. MSUD due to deficiency in E3 subunit
Classic MSUD
• Clinical:– 1st week: poor feeding and vomiting lethargy
coma– Convulsions occur in most infants– Labs: metabolic acidosis
Classic MSUD• Diagnosis:– Definitive: Amino acid analysis shows ↑ leucine,
isoleucine, valine– Peculiar odor of maple syrup in urine, sweat, and
cerumen– Urine: (+) amino acids and their respective ketoacids– Qualitative test:
• Add 2,4-dinitrophenylhydrazine reagent (0.1% in 0.1 N HCl) to urine
• Formation of a yellow precipitate (2,4-dihydrophenylhydrazone) yields a positive test
– Hypomyelination may be seen in neuroimaging
Classic MSUD
• Treatment:– In acute phase:• Adequate hydration• Quick removal of metabolites via Peritoneal Dialysis• Response: significant ↓plasma levels w/n 24 hrs• May develop cerebral edema, treated with mannitol
– After acute phase:• Diet low on branched chain amino acids• Remain on diet for the rest of their lives• Liver transplant shows promising results
Classic MSUD
• Prognosis:– Prognosis remains guarded– May develop the following in stressful conditions
(infection/surgery)• Severe ketoacidosis, cerebral edema, death
– Mental and neurologic deficits are common sequelae
Genetics of MSUD
• Autosomal recessive• Prevalence of 1 / 185,000• Classic form is more prevalent
LABORATORIES
CBC
• Hgb: 99• Hct: 0.282• WBC: 3.99– Segmenters: 0.46– Monocytes: 0.15– Eosinophils: 0.003– Lypmhocytes: 0.003– Basophils: 0.374
• Plt: 14.8
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