Diagnosis: Maple Syrup Urine Disease (MSUD)
The diagnosis is C. Maple syrup urine disease (MSUD), based on the classic triad of generalized seizures, hypoglycemia, and ketones in urine with a characteristic sweet/burnt sugar odor in a neonate or infant. 1, 2
Clinical Reasoning
Key Diagnostic Features of MSUD
- Characteristic odor is pathognomonic for MSUD, described as maple syrup, burnt sugar, or caramelized smell emanating from cerumen and urine 1, 3
- Neurological manifestations include generalized seizures, lethargy, opisthotonos, and developmental delay occurring in the first 2 weeks of life in classic presentations 4, 2
- Ketonuria is consistently present due to accumulation of branched-chain ketoacids (BCKAs) that cannot be metabolized 1, 4
- Hypoglycemia occurs as a metabolic consequence of the enzyme deficiency affecting branched-chain amino acid metabolism 5
Why Not the Other Options
Galactosemia (Option A) presents with jaundice, hepatomegaly, cataracts, and reducing substances in urine after milk feeding—but no characteristic odor 6
Phenylketonuria (Option B) is typically asymptomatic in the neonatal period and presents later with developmental delay and musty/mousy odor—not in acute crisis with seizures and hypoglycemia 1
Fatty acid oxidation defects (Option D) cause hypoketotic hypoglycemia (low or absent ketones), which is the opposite of this presentation showing ketones in urine 6
Pathophysiology
- MSUD results from deficiency in the branched-chain α-ketoacid dehydrogenase complex, preventing metabolism of leucine, isoleucine, and valine 1
- Accumulation of branched-chain amino acids (BCAAs) and their ketoacid derivatives causes acute neurotoxicity through disruption of glutamate, glutamine, and GABA production 4
- Classic presentation occurs between 2-14 days of life (mean 5 days) with feeding difficulties, failure to thrive, and the pathognomonic maple syrup odor 3
Diagnostic Confirmation
- Urine testing with ferric chloride (FeCl3) and 2,4-dinitrophenylhydrazine (DNPH) provides rapid qualitative screening showing positive ketones 5
- Plasma amino acid analysis reveals markedly elevated leucine, isoleucine, and valine levels (>1000 μmol/L) 2, 3
- Gas chromatography-mass spectrometry confirms increased branched-chain amino acids and detects alloisoleucine, the pathognomonic marker 1, 5
Critical Clinical Pitfall
The burnt sugar odor is the single most important clinical clue—81% of patients exhibit this finding 3. Any newborn presenting as "septic" with feeding difficulties, failure to regain birth weight, or unexplained neurological symptoms must have urine tested for ketones, and if positive, immediate plasma leucine/isoleucine measurement is mandatory 3.