glycogen storage disease type 0

Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia.

Sixteen different mutations have been identified to 2010 in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver.

Glycogen storage disease type 0 (GSD0) is an autosomal recessive disease presenting in infancy or early childhood caused by mutations in the GYS2, a gene located on chromosome 12p 12.2 composed of 16 exons which codes for the hepatic isoform of glycogen synthase (GS).

This rate-limiting enzyme of 80.9 kDa participates in the production of glycogen, the glucose polymer which constitutes the major repository of readily available energy.

Etiology

 germline mutation in the glycogen synthase 2

Physiopathology

Glucose use is strictly controlled and abnormal glucose handling is associated with some human diseases, such as glycogen storage diseases and diabetes.

GS is a key component of the hepatic synthesis of glycogen, catalyzing the successive addition of α-1,4-linked glucose residues to the nonreducing end of glycogen.

Impaired activity of GS results in great reduction of glycogen storage in the liver, which renders the patient prone to develop ketotic hypoglycemia and low lactatemia after prolonged fasting.

The inability to synthesize hepatic glycogen shifts meal-derived glucose from glycogenesis to the glycolytic pathway and explains the findings of hyperglycemia, hyperlactatemia and hyperlipidemia in the postprandial period.

The current gold standard for diagnosis is molecular analysis of the affected gene, which replaced liver biopsy. Sixteen different mutations have been identified to date.

References

 A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0. Soggia AP, Correa-Giannella ML, Fortes MA, Luna AM, Pereira MA. BMC Med Genet. 2010 Jan 5;11:3. PMID: 20051115 (Free)