A 5-day-old male infant is brought to the emergency department by his parents due to 24 hours of decreased feeding, progressive lethargy, and recurrent vomiting. He was born full-term via an uncomplicated vaginal delivery and was discharged home on day 2 of life. The infant is exclusively breastfed. Vital signs show a temperature of 36.2°C (97.2°F), heart rate of 175/min, and respiratory rate of 68/min. On physical examination, the infant is somnolent with diffuse hypotonia and deep, rapid breathing. Laboratory results are as follows:
| Laboratory Test | Result |
|---|---|
| Serum sodium | 139 mEq/L |
| Serum potassium | 4.8 mEq/L |
| Serum chloride | 101 mEq/L |
| Serum bicarbonate | 8 mEq/L |
| Blood glucose | 42 mg/dL |
| Serum ammonia | 450 µmol/L (normal: 15–50 µmol/L) |
Urinalysis is strongly positive for ketones. Deficient activity of which of the following enzymes is the most likely cause of this patient's condition?
- Methylmalonyl-CoA mutaseAnswer
- BOrnithine transcarbamylase
- CMedium-chain acyl-CoA dehydrogenase
- DAldolase B
- EPhenylalanine hydroxylase
Answer
Methylmalonyl-CoA mutase
The correct answer identifies the enzyme deficient in methylmalonic acidemia, a classic organic acidemia. This infant presents with lethargy, poor feeding, and Kussmaul respirations alongside a profound high anion gap metabolic acidosis (), prominent ketonuria, hypoglycemia, and hyperammonemia. This combination is the hallmark of an organic acid accumulation. Methylmalonyl-CoA mutase normally converts methylmalonyl-CoA to succinyl-CoA. In its absence, organic acids accumulate and secondarily inhibit the urea cycle (causing hyperammonemia) and gluconeogenesis (causing hypoglycemia).
Step-by-Step Solution
Key Concept
Neonatal organic acidemias (e.g., methylmalonic acidemia) typically present with a severe high anion gap metabolic acidosis, massive ketosis, hyperammonemia, and hypoglycemia, which distinguishes them biochemically from urea cycle defects and fatty acid oxidation disorders.