A neonate presents with severe hypoglycemia, metabolic acidosis, marked elevation of blood lactate, pyruvate, and alanine, along with apnea and abnormal neurological signs. Urinary organic acids show elevated citrate, alpha-ketoglutarate, and fumarate. Deficiency of which enzyme best explains this picture?
- A Pyruvate dehydrogenase complex
- B Pyruvate carboxylase ✓
- C Pyruvate kinase
- D Alanine aminotransferase
Correct answer: B. Pyruvate carboxylase
Explanation
Pyruvate carboxylase, a biotin-dependent mitochondrial enzyme, converts pyruvate to oxaloacetate and is the first committed step of gluconeogenesis. Its deficiency blocks both gluconeogenesis and anaplerotic entry into the TCA cycle, so pyruvate accumulates and is diverted to alanine and lactate. TCA cycle intermediates such as citrate and alpha-ketoglutarate fall relative to upstream accumulation patterns. Pyruvate dehydrogenase deficiency raises lactate but spares gluconeogenesis, so fasting hypoglycemia is not a feature.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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