Type III Glycogen Storage Disease (Cori Disease) Flashcards
A 10-year-old boy is evaluated for persistent muscle cramps and fatigue after exercise. On physical examination, he has hepatomegaly and mild ascites. Laboratory studies reveal mild fasting hypoglycemia, hyperlipidemia, and normal blood lactate levels. A liver biopsy shows cytosolic accumulation of glycogen with short outer branches. Genetic testing confirms a mutation in the AGL gene. Which of the following is the most likely diagnosis?
A) Von Gierke disease
B) Pompe disease
C) Cori disease
D) McArdle disease
E) Anderson disease
Answer: Cori disease
Explanation: Cori disease (Type III glycogen storage disease) is caused by a deficiency of the glycogen debranching enzyme due to mutations in the AGL gene. The enzyme is responsible for hydrolyzing α-1,6 linkages and transferring glycogen branches for efficient breakdown. Its deficiency leads to the accumulation of limit dextrin-like complexes in the cytosol. Clinical features include hepatomegaly, mild fasting hypoglycemia, muscle weakness, and hyperlipidemia. Unlike Von Gierke disease, gluconeogenesis is functional, and blood lactate levels remain normal.
Incorrect Answers:
A) Von Gierke disease presents with severe fasting hypoglycemia, hyperuricemia, and lactic acidosis, not normal blood lactate levels.
B) Pompe disease primarily causes cardiomyopathy, hypotonia, and respiratory failure, not significant hypoglycemia.
D) McArdle disease (Type V) is characterized by exercise intolerance and myoglobinuria, with no liver involvement.
E) Anderson disease (Type IV) leads to progressive liver cirrhosis due to defective glycogen branching enzyme, not the debranching enzyme.
What is the gene defect and deficient enzyme in Cori disease (Type III glycogen storage disease)?
Mutation in the AGL gene on chromosome 1p; deficient enzyme is the glycogen debranching enzyme (α-1,6-glucosidase and 4-α-D-glucanotransferase
What is the primary mode of inheritance for Cori disease?
Autosomal recessive inheritance
What is the role of the glycogen debranching enzyme in Cori disease?
Performs two functions in glycogenolysis: hydrolyzes α-1,6 linkages and transfers outer branches to a longer chain for glycogen breakdown
What are the characteristic muscular symptoms of Cori disease?
Generalized muscle weakness and/or cramps
What are the characteristic hepatic symptoms of Cori disease?
Possibly cirrhosis, hepatomegaly, ascites, and splenomegaly
What are the key metabolic abnormalities in Cori disease?
Fasting hypoglycemia.
Ketosis.
Hepatomegaly.
Hyperlipidemia.
Cytosolic accumulation of limit dextrin-like complexes.
How does Cori disease differ from Von Gierke disease in terms of gluconeogenesis?
Gluconeogenesis is functional in Cori disease, unlike Von Gierke disease, where it is impaired
Cori disease (type III) has normal lactate levels, unlike Von Gierke disease (type I).
What complications are associated with Cori disease?
Type III may result in cardiomyopathy
How is Cori disease managed?
Maintain glucose levels with cornstarch or commercial glucose polymers.
