Clinical scenario: vomiting | rapid breathing | acidosis | hyperammonemia
A 12-day-old exclusively breastfed neonate is brought to the emergency department with poor feeding, vomiting, lethargy, and rapid breathing. He is initially treated with intravenous antibiotics for presumed pneumonia, but his respiratory distress worsens despite a normal chest radiograph and sterile blood cultures. Arterial blood gas reveals pH 7.12, HCO₃⁻ 8 mmol/L, and a high anion gap metabolic acidosis. Serum ammonia is 340 μmol/L (normal <100 μmol/L). Urine ketones are positive, and blood glucose is normal.
Which of the following is the most likely diagnosis?
A. Maple syrup urine disease
B. Methylmalonic acidemia
C. Propionic acidemia
D. Pyruvate dehydrogenase deficiency
E. Urea cycle disorder
Correct answer & Explanation:
Correct Answer:
C. Propionic acidemia
Explanation
Propionic acidemia is an autosomal recessive organic acidemia caused by propionyl-CoA carboxylase deficiency.
Neonates typically present within the first 1–2 weeks of life with:
- Poor feeding
- Vomiting
- Lethargy
- Hypotonia
- Kussmaul (deep, rapid) breathing
- Encephalopathy
The respiratory distress is secondary to severe metabolic acidosis, leading to frequent initial misdiagnosis as pneumonia or neonatal sepsis.
Characteristic laboratory findings include:
- High anion gap metabolic acidosis
- Hyperammonemia
- Ketosis
- Elevated propionylcarnitine (C3)
- Increased urinary 3-hydroxypropionate and methylcitrate
Immediate management includes:
- Stop protein intake temporarily
- High-calorie intravenous glucose ± lipids to reverse catabolism
- Correct metabolic acidosis
- Ammonia-lowering therapy (e.g., sodium benzoate or hemodialysis if severe)
- Carnitine supplementation
- Long-term protein restriction with specialized metabolic formula
Why the other options are incorrect
- A. Maple syrup urine disease – Causes encephalopathy and ketoacidosis but is characterized by elevated branched-chain amino acids and the classic maple syrup odor. Hyperammonemia is usually less prominent than in organic acidemias.
- B. Methylmalonic acidemia – Also causes high anion gap metabolic acidosis with hyperammonemia and is a close differential. However, diagnosis is confirmed by markedly elevated methylmalonic acid in plasma/urine. The elevated C3 acylcarnitine pattern overlaps with propionic acidemia, making biochemical confirmation essential.
- D. Pyruvate dehydrogenase deficiency – Causes lactic acidosis and neurological impairment but hyperammonemia is not a typical feature.
- E. Urea cycle disorder – Causes marked hyperammonemia, but metabolic acidosis and ketosis are typically absent. Instead, patients usually have respiratory alkalosis due to central hyperventilation.
MRCPCH High-Yield Pearl
A neonate with “pneumonia” who has a normal chest X-ray, persistent tachypnea, encephalopathy, hyperammonemia, and a high anion gap metabolic acidosis should immediately raise suspicion for an organic acidemia (especially propionic acidemia or methylmalonic acidemia), not a primary respiratory disorder.
References
- Nelson Textbook of Pediatrics, 22nd Edition
- Saudubray JM. Inborn Metabolic Diseases, 7th Edition
- GeneReviews®: Propionic Acidemia
