Current Molecular Medicine - Volume 2, Issue 2, 2002

Glycogen is a branched polymer of glucose which serves as a reservoir of glucose units. The two largest deposits in mammals are in the liver and skeletal muscle but many cells are capable synthesizing glycogen. Its accumulation and utilization are under elaborate controls involving primarily covalent phosphorylation and allosteric ligand binding. Both muscle and liver glycogen reserves are important for whole body glucose m Read More

Glycogen storage disease type I (GSD-I) is a group of autosomal recessive disorders with an incidence of 1 in 100,000. The two major subtypes are GSD-Ia (MIM232200), caused by a deficiency of glucose-6-phosphatase (G6Pase), and GSD-Ib (MIM232220), caused by a deficiency in the glucose-6-phosphate transporter (G6PT). Both G6Pase and G6PT are associated with the endoplasmic reticulum (ER) membrane. G6PT translocate Read More

Glycogenosis type II (GSDII, Pompe disease) is an autosomal recessive lysosomal storage disease caused by a deficiency of acid α-glucosidase (acid maltase, GAA). The enzyme degrades a -1,4 and α -1,6 linkages in glycogen, maltose, and isomaltose. Deficiency of the enzyme results in accumulation of glycogen within lysosomes and in cytoplasm eventually leading to tissue destruction.The discovery of the acid a-glucosi Read More

Deficiency of the glycogen debranching enzyme (gene, AGL) causes glycogen storage disease type III (GSD-III), an autosomal recessive disease affecting glycogen metabolism. Most GSDIII patients have AGL deficiency in both the liver and muscle (type IIIa), but some have it in the liver but not muscle (type IIIb). Cloning of human AGL cDNAs and determination of the genomic structure and mRNA isoforms of AGL have allow Read More

Glycogen storage disease type IV (GSD-IV), also known as Andersen disease or amylopectinosis (MIM 23250), is a rare autosomal recessive disorder caused by a deficiency of glycogen branching enzyme (GBE) leading to the accumulation of amylopectin-like structures in affected tissues. The disease is extremely heterogeneous in terms of tissue involvement, age of onset and clinical manifestations. The human GBE cDNA is ap Read More

McArdle disease, one of the most common metabolic causes of exercise intolerance and recurrent myoglobinuria, is due to biochemical defects of the muscle isoform of glycogen phosphorylase. The gene for myophosphorylase (PGYM) is on chromosome 11, and 33 distinct mutations have been identified in patients from all over the world. In Caucasians, a nonsense mutation in exon 1 (R49X) is common enough to warrant screen Read More

Phosphofructokinase deficiency (Tarui disease, glycogen storage disease VII, GSD VII) stands out among all the GSDs. PFK deficiency was the first recognized disorder that directly affects glycolysis. Ever since the discovery of the disease in 1965, a wide range of biochemical, physiological and molecular studies of the disorder have greatly expanded our understanding of the function of normal muscle, general control of glycolys Read More

Fanconi-Bickel syndrome (FBS, OMIM 227810) is a rare type of glycogen storage disease (GSD). It is caused by homozygous or compound heterozygous mutations within GLUT2, the gene encoding the most important facilitative glucose transporter in hepatocytes, pancreatic b-cells, enterocytes, and renal tubular cells. To date, 112 patients have been reported in the literature. Most patients have the typical combinati Read More