MCQ: recurrent vomiting | lethargy | hypotonia | hyperammonemia
A 7-day-old previously healthy term infant is admitted with poor feeding, recurrent vomiting, excessive sleepiness, and intermittent episodes of hyperventilation for the past 24 hours. He has received intravenous antibiotics for presumed neonatal sepsis without improvement. On examination, he is lethargic and hypotonic with no dysmorphic features or hepatomegaly.
Investigations show:
- Serum ammonia: 860 μmol/L (normal <100 μmol/L)
- Arterial blood gas: pH 7.54, PaCO₂ 24 mmHg
- Blood glucose: Normal
- Serum lactate: Normal
- Urine ketones: Negative
Which of the following is the most likely metabolic abnormality responsible for this presentation?
A. Elevated argininosuccinic acid
B. Elevated plasma citrulline
C. Elevated plasma leucine
D. Elevated urinary methylmalonic acid
E. Elevated urinary orotic acid
Correct answer & Explanation:
Correct Answer:
B. Elevated plasma citrulline
Explanation: Urea cycle defect
This infant has a urea cycle disorder, suggested by:
- Neonatal onset after protein feeding
- Severe hyperammonemia
- Respiratory alkalosis
- Normal glucose
- Normal lactate
- Absence of ketosis
The most likely diagnosis is Citrullinemia Type I, caused by argininosuccinate synthetase (ASS1) deficiency.
The hallmark biochemical finding is:
- Markedly elevated plasma citrulline
Why the other options are incorrect
- A. Elevated argininosuccinic acid → Seen in argininosuccinate lyase (ASL) deficiency (argininosuccinic aciduria).
- C. Elevated plasma leucine → Characteristic of maple syrup urine disease.
- D. Elevated urinary methylmalonic acid → Seen in methylmalonic acidemia, which presents with high anion gap metabolic acidosis, not isolated respiratory alkalosis.
- E. Elevated urinary orotic acid → Characteristic of ornithine transcarbamylase (OTC) deficiency. While orotic acid may be mildly increased in some distal urea cycle defects, it is not the hallmark finding for citrullinemia.
High-Yield Table for MRCPCH/FCPS
| Disorder | Ammonia | Acid–Base Status | Hallmark Biochemical Finding |
|---|---|---|---|
| OTC deficiency | ↑↑↑ | Respiratory alkalosis | ↑ Urinary orotic acid, ↓ citrulline |
| CPS I deficiency | ↑↑↑ | Respiratory alkalosis | Normal/low urinary orotic acid |
| Citrullinemia Type I | ↑↑↑ | Respiratory alkalosis | ↑↑ Plasma citrulline |
| Argininosuccinic aciduria | ↑↑↑ | Respiratory alkalosis | ↑ Argininosuccinic acid |
| Propionic acidemia | ↑ | Metabolic acidosis | ↑ C3 acylcarnitine, ketosis |
