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