Cori disease (Type IIIa) is due to deficiency of which enzyme?

• A. Glycogen debranching enzyme
• B. Glycogen phosphorylase
• C. Branching enzyme
• D. Lysosomal alpha-glucosidase

Answer: (A)

The idea tested here is which enzyme failure underlies Cori disease and how that affects glycogen breakdown. Glycogenolysis needs two coordinated activities on each branch: a transfer of a small segment to a nearby chain, and then the removal of the remaining single glucose at the branch point by an alpha-1,6-hydrolysis. This debranching step is performed by the glycogen debranching enzyme, which has both a 4:4 transferase function and an alpha-1,6-glucosidase function. When this enzyme is deficient, glycogen can’t be fully degraded beyond short outer branches, so limit dextrin–like structures accumulate in the cytosol, especially in liver and muscle.

In Cori disease (Type IIIa), the lack of glycogen debranching enzyme leads to fasting hypoglycemia and hepatomegaly, with some muscle involvement. This contrasts with other disorders: a deficiency in glycogen phosphorylase causes exercise intolerance without the liver findings typical of Cori; a branching enzyme deficiency results in abnormally branched, poorly structured glycogen and severe infant liver disease; a lysosomal enzyme deficiency causes glycogen accumulation within lysosomes (Pompe disease), with cardiomyopathy as a prominent feature. So the enzyme whose deficiency best explains Cori disease is the glycogen debranching enzyme.