Instituto Valenciano de Microbiología

Masía El Romeral
Ctra. de Bétera a San Antonio Km. 0.3
46117 Bétera (Valencia)
Phone. 96 169 17 02
Fax 96 169 16 37
CIF B-96337217


Glycogen storage disease type III, Cori Disease (Glycogen storage disease type III, Cori disease) - Gen AGL.

Type III glycogen storage disease (also called GSDIII or Cori disease) is an inherited disorder caused by the accumulation of glycogen in the body cells. Accumulated glycogen is structurally abnormal and impairs the function of certain organs and tissues, especially the liver and muscles. Type III glycogen storage is divided into IIIa, IIIb, IIIc and IIId types, which differ in their pattern of signs and symptoms. IIIa and IIIc types primarily affect the liver and muscles. IIIb and IIId types generally only affect the liver. It is very difficult to distinguish the types that affect the same tissues. IIIa and IIIb types are the most common forms of this disease.

This disease is manifested from childhood. People with any GSDIII may have hypoglycemia, hyperlipidemia, and high levels of liver enzymes. Generally, as children grow, they develop hepatomegaly. Liver size is normal during adolescence, but some affected individuals subsequently develop cirrhosis and failure. Often, people with GSDIII have slow growth because of liver problems, which can lead to short stature. In addition, a small percentage of people can develop adenomas in the liver. Other signs and symptoms may include myopathy, hypotonia, myopathy and cardiomyopathy.

This process is due to mutations in the AGL gene, located on the short arm of chromosome 1 (1p21). This gene encodes the enzyme glycogen debranching, involved in the breakdown of glycogen. Glycogen is composed of several glucose molecules. Some glucose molecules are linked together in a straight line, while other branch and form side chains. The debranching enzyme glycogen is involved in the breakdown of these side chains. The AGL gene encodes several isoforms of glycogen debranching enzyme. These isoforms vary according to size and are expressed in different tissues.

Approximately 100 have been identified mutations in the gene responsible for AGL glycogenosis type III. Most of these mutations lead to a premature stop signal encoding the enzyme, which results in a nonfunctional enzyme. As a result, the side chains of the molecules can not be broken glycogen and glycogen molecules accumulate inside the cell. An abnormal accumulation of glycogen causes damage to organs and tissues throughout the body, particularly in the liver and muscles, leading to the signs and symptoms of GSDIII. Mutations in the gene AGL can affect different isoforms of the enzyme, depending on where gene mutations are located. For example, mutations occurring in exon 3 of the gene AGL affect isoform is mainly expressed in the liver. These mutations almost always lead to type GSD IIIb, which is characterized by liver problems.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with glycogen storage disease type III, by complete PCR amplification of exons AGL gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).