Glycogen storage disease type I
USMLE Step 1Difficulty: mediumLast updated:
A 5-month-old girl is evaluated after a seizure that occurred when she slept through a night feeding. Point-of-care glucose was 28 mg/dL. She has a protuberant abdomen with marked hepatomegaly; the spleen is not enlarged. Laboratory studies show lactic acidosis, serum triglycerides of 880 mg/dL, and uric acid of 9.4 mg/dL. Muscle tone and creatine kinase are normal.
Deficiency of which of the following enzymes is the most likely cause?
Answer and explanation
Correct answer: E. Glucose-6-phosphatase
Severe fasting hypoglycemia, lactic acidosis, hepatomegaly, hypertriglyceridemia, and hyperuricemia in an infant are characteristic of glycogen storage disease type I (von Gierke disease). The source's table describes GSD I as presenting before 1 year with severe hypoglycemia, lactic acidosis, and hepatomegaly. Later features include hepatic adenomas, renomegaly, short stature, hypertriglyceridemia, hyperuricemia, and platelet dysfunction. The most common subtype, Ia (more than 80%), is caused by glucose-6-phosphatase deficiency. Without this enzyme, the liver cannot release free glucose from either glycogenolysis or gluconeogenesis, and the trapped glucose-6-phosphate is shunted toward lactate, triglyceride, and uric acid production. Treatment uses frequent feeds, including nocturnal feedings and uncooked cornstarch, to maintain normoglycemia.
Each option explained
- A. Lysosomal acid alpha-glucosidaseIncorrect. Lysosomal acid alpha-glucosidase deficiency (Pompe disease) causes cardiomyopathy and hypotonia, not severe hypoglycemia.
- B. Glycogen debranching enzymeIncorrect. Debranching enzyme deficiency (Cori disease) causes milder hypoglycemia without marked lactic acidosis, often with myopathy and elevated CK.
- C. Muscle glycogen phosphorylaseIncorrect. Muscle phosphorylase deficiency (McArdle disease) causes exercise intolerance and cramps, not infant hypoglycemia.
- D. Galactose-1-phosphate uridyltransferaseIncorrect. GALT deficiency (classic galactosemia) causes jaundice, cataracts, and liver failure after milk feeding, not this metabolic pattern.
- E. Glucose-6-phosphataseCorrect. Glucose-6-phosphatase deficiency (GSD Ia) causes fasting hypoglycemia, lactic acidosis, hepatomegaly, hypertriglyceridemia, and hyperuricemia.
Key point
Von Gierke disease (glucose-6-phosphatase deficiency): fasting hypoglycemia, lactic acidosis, hepatomegaly, hypertriglyceridemia, and hyperuricemia.
From the source
“GSD I (von Gierke disease) Most common type of GSD I: Ia ( > 80%) Onset: Before 1 year Clinical features: Before 1 year, severe hypoglycemia, lactic acidosis, and hepatomegaly”