Glycogen storage disease type 3

Synonyms

9

Overview

Glycogen storage disease type III (also known as GSDIII or Cori disease) is an inherited disorder caused by the buildup of a complex sugar called glycogen in the body's cells. The accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles.

GSDIII is divided into types IIIa, IIIb, IIIc, and IIId, which are distinguished by their pattern of signs and symptoms. GSD types IIIa and IIIc mainly affect the liver and muscles, and GSD types IIIb and IIId typically affect only the liver. It is very difficult to distinguish between the types of GSDIII that affect the same tissues. GSD types IIIa and IIIb are the most common forms of this condition.

Symptoms

Beginning in infancy, individuals with any type of GSDIII may have

low blood sugar (hypoglycemia)
excess amounts of fats in the blood (hyperlipidemia)
elevated blood levels of liver enzymes

As they get older, children with this condition typically develop an

• enlarged liver (hepatomegaly)

Liver size usually returns to normal during adolescence, but some affected individuals develop chronic liver disease (cirrhosis) and liver failure later in life.

People with GSDIII often have slow growth because of their liver problems, which can lead to short stature.

In a small percentage of people with GSDIII, noncancerous (benign) tumors called adenomas may form in the liver.

Individuals with GSDIIIa may develop

• muscle weakness (myopathy) later in life. These muscle problems can affect both heart (cardiac) muscle and the muscles that are used for movement (skeletal muscles). Muscle involvement varies greatly among affected individuals.

The first signs and symptoms are typically

• poor muscle tone (hypotonia)
• mild myopathy in early childhood

The myopathy may become severe by early to mid-adulthood.

Some people with GSDIIIa have a weakened heart muscle (cardiomyopathy), but affected individuals usually do not experience heart failure. Other people affected with GSDIIIa have no cardiac muscle problems.

 

Causes

Mutations in the AGL gene cause GSDIII. The AGL gene provides instructions for making the glycogen debranching enzyme. This enzyme is involved in the breakdown of glycogen, which is a major source of stored energy in the body. Between meals the body breaks down stores of energy, such as glycogen, to use for fuel.

Most AGL gene mutations lead to the production of a nonfunctional glycogen debranching enzyme. These mutations typically cause GSD types IIIa and IIIb. The mutations that cause GSD types IIIc and IIId are thought to lead to the production of an enzyme with reduced function. All AGL gene mutations lead to storage of abnormal, partially broken down glycogen molecules within cells. A buildup of abnormal glycogen damages organs and tissues throughout the body, particularly the liver and muscles, leading to the signs and symptoms of GSDIII.

Diagnosis

Diagnosis depends on patient history and physical examination, muscle biopsy, electromyelography, ischemic forearm test, and creatine kinase levels. Biochemical assay for enzyme activity is the method of definitive diagnosis.

Treatment

Treatment may involve a high protein diet, in order to facilitate gluconeogenesis.