Question

A biopsy is done on a child with an enlarged liver and shows accumulation of glycogen granules with single glucose residues remaining at the branch points near the periphery of the granule. The most likely genetic defect is in the gene encoding: (A) \(\quad a-1,4\) phosphorylase (glycogen phosphorylase). (B) \(\quad a-1,4: a-1,6\) transferase (branching enzyme). (C) \(\quad a-1,4: a-1,4\) transferase (part of debranching enzyme complex) (D) \(\quad \alpha-1,6\) glucosidase (part of debranching enzyme complex).

Short answer

D: \( α-1,6 \) glucosidase

Step-by-step solution

Understand the Problem

The problem involves identifying a genetic defect based on the description of glycogen accumulation in a child's liver biopsy.

Identify Glycogen Structure and Metabolism

Glycogen is composed of glucose molecules connected by \( α-1,4 \) glycosidic bonds with branches formed by \( α-1,6 \) glycosidic bonds. Enzymes involved in glycogen metabolism include glycogen phosphorylase, branching enzyme, and components of the debranching enzyme complex.

Analyze the Findings

The biopsy shows glycogen with single glucose residues left at the branch points. This indicates a defect in debranching, as debranching enzymes are responsible for removing these residues.

Match Findings to Enzyme Defects

Out of the given options, the enzyme \( α-1,6 \) glucosidase is a part of the debranching enzyme complex and specifically removes single glucose residues at \( α-1,6 \) branch points.

Conclusion

Based on the analysis, the most likely genetic defect is in the gene encoding \( α-1,6 \) glucosidase.

Key concepts

Genetic Defect

A genetic defect refers to an abnormality in the DNA sequence of a gene. This can lead to incorrect or dysfunctional proteins. In the context of glycogen storage diseases, a genetic defect might cause a vital enzyme involved in glycogen metabolism to malfunction. When we specify that a child has an enlarged liver due to glycogen storage, it suggests an enzyme crucial for breaking down glycogen is not working properly. For instance, if the enzyme α-1,6 glucosidase (part of the debranching enzyme complex) is defective, glycogen cannot be fully processed, causing an accumulation of incomplete glycogen structures.

Glycogen Metabolism

Glycogen metabolism is the process by which the body stores and breaks down glycogen to release glucose, which cells use for energy. Glycogen is a branched polymer of glucose molecules. Two main types of bonds connect glucose units in glycogen:

• α-1,4 glycosidic bonds link glucose units linearly.
• α-1,6 glycosidic bonds form branch points.

Various enzymes are responsible for glycogen synthesis and breakdown. Glycogen phosphorylase breaks α-1,4 bonds to release glucose-1-phosphate. Meanwhile, the debranching enzyme complex, including α-1,4:α-1,4 transferase and α-1,6 glucosidase, handles branch removal. Any defect in these enzymes can disrupt normal glycogen metabolism, leading to glycogen storage diseases.

Debranching Enzyme Complex

The debranching enzyme complex comprises two critical enzymes that help break down branched glycogen structures:

• α-1,4:α-1,4 transferase moves a block of glucose residues adjacent to a branch point.
• α-1,6 glucosidase removes the single glucose residue left at the branch point.

When there's a defect in any part of this complex, glycogen cannot be fully broken down. The child in the problem has glycogen with single glucose residues at branch points. This suggests a defect in α-1,6 glucosidase, as this enzyme's role is to remove those single glucose residues. Without it, glycogen breakdown remains incomplete, leading to characteristic storage issues.

Biopsy Analysis

A biopsy involves removing a small piece of tissue for examination. In diagnosing glycogen storage diseases, a liver biopsy can be crucial. By examining liver tissue under a microscope, doctors can observe the glycogen structure within the cells.
For the child in the problem, the biopsy showed single glucose residues at the branch points of glycogen molecules. This is a strong indication of a defect in the glycogen debranching process.

Through this microscopic examination, scientists and doctors can link specific glycogen storage patterns with potential enzyme deficiencies. It helps in pinpointing the exact genetic defect, leading to accurate diagnosis and management of the disease.