The enzyme defect in von Gierke&;s disease (type-1 glycogen storage disease) is
## Core Concept
Von Gierke's disease, also known as type I glycogen storage disease, is a genetic disorder caused by a deficiency in an enzyme involved in glycogenolysis and gluconeogenesis. This condition leads to an inability to convert glycogen to glucose, resulting in severe hypoglycemia and hepatomegaly. The enzyme defect in this disease affects the liver's ability to regulate blood glucose levels.
## Why the Correct Answer is Right
The correct answer, **D. Glucose-6-phosphatase**, is the enzyme that is deficient in von Gierke's disease. Glucose-6-phosphatase is crucial for the final steps of both glycogenolysis and gluconeogenesis, catalyzing the conversion of glucose-6-phosphate to glucose, which can then be released into the bloodstream. A deficiency in this enzyme impairs the liver's ability to produce glucose, leading to the characteristic features of the disease.
## Why Each Wrong Option is Incorrect
- **Option A: Glycogen phosphorylase** is involved in the breakdown of glycogen to glucose-1-phosphate (glycogenolysis) but is not the enzyme deficient in von Gierke's disease. Deficiency in glycogen phosphorylase leads to McArdle's disease (type V glycogen storage disease).
- **Option B: Debranching enzyme** is another enzyme involved in glycogenolysis, specifically in the breakdown of glycogen's branched structures. A deficiency in debranching enzyme leads to Cori's disease (type III glycogen storage disease).
- **Option C: Phosphoglucomutase** plays a role in glycogen synthesis and glycogenolysis, converting glucose-1-phosphate to glucose-6-phosphate, but it is not the enzyme deficient in von Gierke's disease.
## Clinical Pearl / High-Yield Fact
A key clinical feature of von Gierke's disease is the presence of **severe hypoglycemia**, **hepatomegaly**, and **lactic acidosis**. Patients often have a characteristic "doll-like" face and may experience growth retardation. A critical aspect to remember is that these patients are at risk for developing **hepatic adenomas** and **gout**.
## Correct Answer: D. Glucose-6-phosphatase