Glycogen Storage Disease Type III (GSD III)

At a glance

Inherited metabolic disease resulting in accumulation of abnormal glycogen in different tissues of the body. Glycogen storage disease Type III (Cori Disease) is an autosomal recessive metabolic disorder and inborn error of metabolism characterized by a deficiency in glycogen debranching enzymes. There are four different types based on the clinical presentation. It presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly, muscular disease, hypotonia, and often severe cardiomyopathy usually occurring later. The hepatomegaly and splenomegaly regress at adolescence.

Synonyms

Cori Disease; Forbes Disease; Illingworth-Cori-Forbes Disease; Amylo-1,6-Glucosidase Debrancher Deficiency; Glycogenosis III; Debranching Enzyme Deficiency; Limit Dextrinosis Syndrome.

History

It is also known as Cori’s disease in honor of the 1947 Nobel laureates Carl Cori (1896-1984), a Czech American biochemist, Gerty Cori (1896-1957), a Jewish Czech American biochemist, and Bernardo Alberto Houssay, an Argentinian physiologist. Other names include Forbes disease in honor of clinician Gilbert Burnett Forbes (1915-2003), an American Physician, who further described the features of the disorder, and limit dextrinosis, due to the dysfunction of dextrin-like structures in cytosol.

Classification

Based on the clinical manifestations, Glycogen Storage Disease Type III is divided into four classes:

• GSD IIIa: Most common, (along with GSD IIIb) and which clinically includes muscle and liver involvement

• GSD IIIb: Clinically has liver involvement but no muscle involvement

• GSD IIIc: Clinically affects liver and muscle

• GSD IV: Affects liver only (not muscle)

Incidence

Incidence of GSD Type III in the United States and other countries is estimated to make up for 24% of all patients affected with GSD. It occurs in about 1 of every 100,000 live births.

Genetic inheritance

Autosomal recessive. The responsible defect has been mapped to 1p21.

Pathophysiology

Deficiency of amylo-1,6-debrancher enzyme, an enzyme found in all tissues, that converts glycogen to glucose-1,6-phosphate, resulting in accumulation of dextrin. The site of glycogen accumulation is primarily cytoplasmic. Disease results from generalized liver and muscle (GSD IIIa) or isolated (liver only) deficiency of glycogen debranching enzyme (GSD IIIb). Limit dextrin is the remaining polymer produced after hydrolysis of glycogen. Without glycogen debranching enzymes to further convert these branched glycogen polymers to glucose, limit dextrinosis abnormally accumulates in the cytoplasm.

Diagnosis

Low blood glucose levels, elevated glycogen content in red blood cells, and elevated levels of fat. Uric acid and lactic acid levels are usually normal. Liver biopsy shows inflammatory changes, significantly abnormally structured glycogen content, and deficiency of the debrancher enzyme. Biopsy of muscle shows an accumulation of abnormally structured glycogen in Type IIIa.

Clinical aspects

Affected organs vary. Moderate-to-marked hepatomegaly. May have ...