Correct Answer: B. Glucose 6 Phosphatase
Glucose 6-phosphatase (G6Pase) deficiency causes Glycogen Storage Disease Type I (GSD-I), also known as Von Gierke disease. This enzyme is located on the endoplasmic reticulum membrane of hepatocytes and is responsible for the final step of both glycogenolysis and gluconeogenesis — converting glucose-6-phosphate (G6P) into free glucose for release into the bloodstream. Without G6Pase, the liver cannot export glucose, leading to profound fasting hypoglycemia despite the liver being loaded with metabolic substrates.
The clinical picture in this child — easy fatigability, increased hunger between meals relieved by eating — is a classic presentation of recurrent hypoglycemia. Because G6Pase is absent, glucose-6-phosphate cannot be converted to free glucose; instead, it is shunted into glycogen synthesis and glycolysis. Over time, the accumulated glycogen and triglycerides cause hepatomegaly. The liver examination finding of no functional glycogen release (glycogen that cannot be mobilized into usable glucose) is the key pathophysiological point: the glycogen is structurally present but metabolically "invisible" to the body because the final export step is blocked. This results in a liver that fails to maintain euglycemia during fasting, explaining the child's hunger and fatigue between meals.
G6Pase deficiency is the most common glycogenosis and a high-yield topic for NEET PG. Associated features include lactic acidosis, hyperuricemia, hyperlipidemia, and a "doll-like" facies with a protuberant abdomen. The hypoglycemia is severe and does not respond to glucagon (since glycogenolysis is intact but G6P cannot exit as glucose).
Why other options are wrong
- A. Debranching enzyme — Deficiency causes GSD-III (Cori disease), which presents with glycogen accumulation of abnormal structure, hepatomegaly, and milder hypoglycemia. Glycogen is present and excessive, not absent or non-functional.
- C. Glycogen synthase — Deficiency causes GSD-0, the only GSD with truly absent hepatic glycogen. However, GSD-0 is extremely rare and presents with fasting hypoglycemia and postprandial hyperglycemia. The clinical scenario here — with hunger between meals and easy fatigability — fits the far more common G6Pase deficiency (GSD-I).
- D. Glycogen phosphorylase — Deficiency causes GSD-V (McArdle disease) in muscle or GSD-VI (Hers disease) in liver. These present with glycogen accumulation, exercise intolerance, and muscle cramps — not the fasting hypoglycemia and hunger pattern described here.