A child presents with massive hepatomegaly and hypoglycemia. There is no improvement in blood glucose on the administration of glucagon. The probable diagnosis is –
**Core Concept**
Glycogen storage diseases (GSDs) are a group of metabolic disorders caused by enzyme deficiencies affecting glycogen synthesis, breakdown, or both. The most relevant GSDs in this context include GSD type I (von Gierke disease) and GSD type III (Cori disease).
**Why the Correct Answer is Right**
The child's presentation of massive hepatomegaly and hypoglycemia, with no improvement in blood glucose on glucagon administration, is suggestive of GSD type I. Glucagon stimulates glycogen breakdown, but in GSD type I, the enzyme glucose-6-phosphatase is deficient, preventing the conversion of glucose-6-phosphate to glucose. This leads to impaired glucose release from glycogen stores, resulting in hypoglycemia despite adequate glycogen stores.
**Why Each Wrong Option is Incorrect**
**Option A:** GSD type III (Cori disease) is characterized by a deficiency of the debranching enzyme amylo-alpha-1,6-glucosidase. While it can cause hepatomegaly and hypoglycemia, glucagon administration typically improves blood glucose levels due to increased glycogen breakdown.
**Option B:** GSD type VI (Hers disease) is caused by a deficiency of liver phosphorylase or phosphorylase kinase. Patients with GSD type VI may exhibit hypoglycemia, but glucagon administration can improve blood glucose levels due to increased glycogen breakdown.
**Option C:** GSD type IV (Andersen disease) is caused by a deficiency of the branching enzyme glycogen branching enzyme. Patients with GSD type IV typically present with cirrhosis and hepatic failure, rather than isolated hypoglycemia.
**Clinical Pearl / High-Yield Fact**
Glucagon administration is a useful diagnostic tool in GSDs, particularly in distinguishing between GSD types I and III. A lack of response to glucagon in a hypoglycemic patient suggests a deficiency of glucose-6-phosphatase, characteristic of GSD type I.
**Correct Answer:** C.