Type IV Glycogen Storage (Andersen) Disease


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Introduction to Andersen Disease

Glycogen storage disease type IV (GSDIV) is also known as Andersen disease or amylopectinosis. Andersen disease is inherited as an autosomal recessive disorder. This disease was originally described by D. Andersen in 1956, hence the association of his name with the disease. The disease was seen in a patient exhibiting progressive hepatosplenomegaly along with the storage of an abnormal glycogen that had poor solubility in the liver. The abnormal glycogen had few branch points with long outer chains containing more α-1,4-linked glucose than the normal polysaccharide which contains both α-1,4- and α-1,6-glycosidic linkages. This resultant structure was similar to that of amylopectin (the structure of starch in plants), thus the associated name of amylopecintosis. Because of the structure of the glycogen it was suspected that there was a deficiency in glycogen branching enzyme activity. This was indeed found to be true in 1966.

Glycogen branching enzyme (gene symbol GBE1), also called amylo-(1,4 to 1,6) transglycosylase, is a monomeric protein. The α-1,6 branches in glucose are produced by this enzyme through a process involving the transfer of a terminal fragment of 6-7 glucose residues (from a polymer at least 11 glucose residues long) to an internal glucose residue at the C-6 hydroxyl position. The GBE1 gene is located on chromosome 3p12.3 and is composed of 16 exons that encode an mRNA of 2,106 bp containing a protein coding region of 702 amino acids.

Reaction catalyzed by glycogen branching enzyme

Reaction catalyzed by glycogen branching enzyme

Clinical Features of Andersen Disease

Analysis of mutants in the branching enzyme gene demonstrated that both hepatic and neuromuscular forms of GSDIV were the result of defects in the same gene. The clinical presentation of GSDIV symptoms usually occurs in the first few months of life and is characterized by hepatosplenomegaly and failure to thrive. The disease progresses liver cirrhosis, portal vein hypertension, esophageal varices and ascites. Death will usually ensue by 5 years of age. Because of the similarities in symptoms between GSDIV and other causes of cirrhosis in infancy it is necessary to carry out a biopsy of the liver and examine for the presence of the associated abnormal glycogen. In addition, assay for branching enzyme deficiency in muscle, leukocytes, erythrocytes, or fibroblasts can be carried out to determine the exact defect resulting in the hepatomegaly. Treatment of GSDIV normally involves maintenance of normal blood glucose along with adequate nutrient intake both of which will improve liver function and muscle strength. In cases of progressive liver failure, transplant may be the only effective option.

 

 

 

 

 

 

 

 

 

 

 


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