Maple Syrup Urine Disorder (MSUD) UPCM Class 2011 Block 9b Tampo, Tanyu, Tiongson, Torio
Jan 15, 2016
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