Accumulation of glycogen in lysosomes is characteristic in the deficiency of
## **Core Concept**
The question tests understanding of lysosomal storage diseases, specifically those involving glycogen accumulation. Lysosomal storage diseases occur due to deficiencies in lysosomal enzymes or proteins, leading to accumulation of substrates within lysosomes. Glycogen storage diseases are a subset of these disorders.
## **Why the Correct Answer is Right**
The correct answer, **D. Acid alpha-glucosidase (GAA)**, is related to Pompe disease (Glycogen Storage Disease Type II). Acid alpha-glucosidase is a lysosomal enzyme crucial for breaking down glycogen into glucose. A deficiency in this enzyme leads to the accumulation of glycogen within lysosomes, particularly in muscle cells, causing Pompe disease. This condition is characterized by the accumulation of glycogen with a structure similar to normal glycogen but with short outer branches.
## **Why Each Wrong Option is Incorrect**
- **Option A:** Deficiency in glucose-6-phosphatase leads to von Gierke's disease (Glycogen Storage Disease Type I), characterized by accumulation of glycogen in hepatocytes and renal tubular cells, but not within lysosomes.
- **Option B:** Debranching enzyme deficiency causes Cori's disease (Glycogen Storage Disease Type III), leading to accumulation of glycogen with long outer branches in the liver, muscles, and heart, but not specifically within lysosomes.
- **Option C:** Phosphorylase deficiency results in McArdle's disease (Glycogen Storage Disease Type V), primarily affecting muscle and leading to an inability to break down glycogen to glucose-1-phosphate, but not involving lysosomal accumulation.
## **Clinical Pearl / High-Yield Fact**
A key point to remember is that Pompe disease is one of the few glycogen storage diseases that involves lysosomal accumulation of glycogen due to the deficiency of a lysosomal enzyme, acid alpha-glucosidase. This disease presents in infants with severe symptoms, including cardiomegaly, and in adults with a milder, progressive myopathy.
## **Correct Answer:** D. Acid alpha-glucosidase.