Glycogenosis type III

Glycogenosis Type III

Glycogenosis Type III, also known as Cori disease or Forbes disease, is a glycogen storage disease (GSD) characterized by a deficiency in the enzyme glycogen debranching enzyme. This enzyme deficiency leads to the accumulation of abnormal glycogen with short outer branches in the liver, muscles, and sometimes the heart, causing a range of symptoms.

Pathophysiology

Glycogen is a polysaccharide that serves as a form of energy storage in animals and fungi. In humans, it is primarily stored in the liver and muscle tissues. The breakdown of glycogen into glucose is a crucial process for maintaining blood sugar levels, especially between meals and during physical activity.

In Glycogenosis Type III, the deficiency of the glycogen debranching enzyme impairs the normal breakdown of glycogen. This enzyme has two activities: 4-alpha-glucanotransferase and amylo-1,6-glucosidase. The deficiency leads to the accumulation of glycogen with short outer branches, which cannot be fully degraded.

Clinical Presentation

Patients with Glycogenosis Type III typically present with:

• Hepatomegaly: Enlargement of the liver due to glycogen accumulation.
• Hypoglycemia: Low blood sugar levels, especially during fasting.
• Hyperlipidemia: Elevated levels of lipids in the blood.
• Growth retardation: Delayed growth in children.
• Muscle weakness: Due to glycogen accumulation in muscle tissues.
• Cardiomyopathy: In some cases, the heart muscle may be affected, leading to cardiac complications.

Diagnosis

Diagnosis of Glycogenosis Type III is based on clinical presentation, biochemical tests, and genetic testing. Key diagnostic steps include:

• Blood tests: To check for hypoglycemia, elevated liver enzymes, and hyperlipidemia.
• Liver biopsy: Histological examination may show glycogen accumulation.
• Enzyme assay: Measurement of debranching enzyme activity in liver or muscle tissue.
• Genetic testing: Identification of mutations in the AGL gene, which encodes the glycogen debranching enzyme.

Management

Management of Glycogenosis Type III focuses on dietary modifications and supportive care:

• Dietary management: Frequent meals rich in carbohydrates to prevent hypoglycemia. Some patients may benefit from a high-protein diet.
• Monitoring: Regular follow-up to monitor growth, liver function, and cardiac health.
• Physical therapy: To maintain muscle strength and function.

Prognosis

The prognosis for individuals with Glycogenosis Type III varies. With appropriate management, many patients can lead relatively normal lives, although some may experience complications such as liver cirrhosis or cardiomyopathy.

Genetics

Glycogenosis Type III is inherited in an autosomal recessive pattern. Mutations in the AGL gene, located on chromosome 1, are responsible for the condition. Genetic counseling is recommended for affected families.

Also see

• Glycogen storage disease
• Glycogenosis type I
• Glycogenosis type II
• Glycogenosis type IV