Type III Glycogen Storage (Cori) Disease
OMIM Link for Cori Disease
Return to The Mobile Medical Biochemistry Page
Introduction to Cori Disease
Glycogen storage disease type III (GSDIII) is also known as Cori disease, Forbes disease and limit dextrinosis. The symptoms associated with GSDIII were first described in 1952 by Illingworth and Cori and was studies clinically by Forbes hence the associated names for this disorder. The disorder is associated with the accumulation of an abnormally structured glycogen having very short outer chains. This structure is similar to what would be seen in a phosphorylase-limit dextrin. The disorder was predicted, and later shown, to be the result of a deficiency of amylo-1,6-glucosidase (AGL), also known as the glycogen debrancher enzyme (GDE).
The amylo-1,6-glucosidase gene (symbol AGL) is located on chromosome 1p21 spanning 85 kb and is composed of 35 exons encoding a protein of 1532 amino acids with a predicted molecular mass of 173 kDa. The enzyme has two distinct catalytic activities, amylo-1,6-glucosidase and 4-α-glucanotransferase. The two activities encompass distinct catalytic sites on the enzyme and can function independent of each other. However, both activities as well as the binding of glycogen are required for complete function. The AGL gene is subject to alternative splicing which generates at least 6 isoforms of the mRNA. The major isoform (isoform 1) of the AGL mRNA begins transcription at exon 1 and translation begins at exon 3. There are at least 3 muscle-specific isoforms which begin transcription at exon 2. There are two promoters for the AGL gene which direct the tissue-specific expression pattern of the various isoforms of AGL mRNA.
Reaction catalyzed by glycogen debranching enzyme
Clinical Features of Cori Disease
Deficiency in glycogen debranching activity causes hepatomegaly, hypoglycemia, variable skeletal myopathy, cardiomyopathy and results in short stature. Patients with both liver and muscle involvement have GSDIIIa and those with only liver involvement (~15% of GSDIII patients) are classified as GSDIIIb. Because heptomegaly, hypoglycemia, hyperlipidemia and growth retardation are common symptoms in both GSDI and GSDIII, it is difficult to initially determine from which disease an infant is suffering. Definitive diagnosis is only made by examining the structure of the glycogen in patients as well as assaying for the level of activity of the debranching enzyme. This diagnosis is best accomplished from liver and/or muscle biopsy. The hepatic symptoms of GSDIII usual resolve after puberty. However, liver failure due to cirrhosis may occur. During periods of hypoglycemia, GSDIII is treated with frequent high carbohydrate meals with cornstarch supplements. A high protein diet is also effective as this drive gluconeogenesis. There is currently no effective treatment for the progressive cardiomyopathy.
return to Glycogen Metabolism page
Return to The Mobile Medical Biochemistry Page
Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu