A 6-month-old male infant is brought to the pediatric emergency department due to poor feeding, lethargy, and seizures. His parents report that he has been irritable and has not been gaining weight as expected. The pregnancy and delivery were uneventful. Vital signs are within normal range. Physical examination reveals hepatomegaly. Laboratory studies show blood glucose of 30 mg/dL (70–100 mg/dL), serum lactate of 5.5 mmol/L (<2.0 mmol/L), elevated uric acid, and hyperlipidemia. A liver biopsy shows increased glycogen content.
A deficiency in which of the following enzymes is most likely responsible for this patient’s condition?
C) Glucose-6-phosphatase
This infant’s presentation of severe hypoglycemia, lactic acidosis, hepatomegaly, hyperuricemia, hyperlipidemia, and increased glycogen content in the liver is consistent with glycogen storage disease type I (von Gierke disease), caused by glucose-6-phosphatase deficiency. This enzyme is critical for the final step of glycogenolysis and gluconeogenesis, converting glucose-6-phosphate to free glucose. Its deficiency leads to glycogen accumulation in the liver, hypoglycemia due to impaired glucose release, and lactic acidosis from shunting of glucose-6-phosphate to glycolysis. Hyperuricemia and hyperlipidemia result from metabolic derangements, including increased purine degradation and impaired lipid clearance.
Answer choice A: Branched-chain alpha-ketoacid dehydrogenase, is incorrect. This deficiency causes maple syrup urine disease, characterized by elevated branched-chain amino acids, ketoacidosis, and neurological symptoms. Hypoglycemia and glycogen accumulation are not features, and hepatomegaly is not typically prominent.
Answer choice B: Galactose-1-phosphate uridyltransferase, is incorrect. This deficiency causes classic galactosemia, presenting with jaundice, hepatomegaly, cataracts, and failure to thrive after galactose ingestion (e.g., milk). Hypoglycemia may occur, but lactic acidosis, hyperuricemia, and glycogen accumulation are not prominent features.
Answer choice D: Ornithine transcarbamylase, is incorrect. Ornithine transcarbamylase deficiency, a urea cycle disorder, causes hyperammonemia, neurological symptoms, and respiratory alkalosis. Hypoglycemia, lactic acidosis, and glycogen accumulation are not associated with this condition.
Answer choice E: Pyruvate kinase, is incorrect. Pyruvate kinase deficiency causes hemolytic anemia due to impaired glycolysis in red blood cells, leading to reduced adenosine triphosphate (ATP) production. It does not cause hypoglycemia, lactic acidosis, or glycogen accumulation in the liver, and hepatomegaly is not a typical feature.
Key Learning Point
Glucose-6-phosphatase deficiency (von Gierke disease) causes glycogen storage disease type I, leading to hypoglycemia, lactic acidosis, hepatomegaly, hyperuricemia, and hyperlipidemia due to impaired glycogenolysis and gluconeogenesis. Diagnosis is confirmed by liver biopsy or genetic testing, and management includes frequent feedings and cornstarch therapy to maintain glucose levels.
