Glycogen Storage Disease Type VI (GSD VI)

Autosomal recessive inborn error of metabolism of glycogen producing a heterogeneous group of hepatic glycogenoses with mild clinical manifestations and benign course.

Glycogen Phosphorylase Deficiency; Hepatic Phosphorylase Kinase Deficiency; Hers Syndrome; Liver Phosphorylase Deficiency; X-Linked Liver Glycogenosis; Glycogenosis type VI; Phosphorylase b Kinase Deficiency.

Inborn error of metabolism consisting of a deficiency of liver phosphorylase (classic form) or other enzyme defects of the phosphorylase cascade system such as phosphorylase b kinase deficiency (formerly GSD IX, GSD VIII by McKusick) and adenosine 3',5'-cyclic monophosphate (cyclic AMP)-dependent protein kinase deficiency (formerly GSD X).

Accounts for about 30% of all GSD, of which approximately 75% result from the X-linked recessive form of phosphorylase kinase deficiency. Incidence up to 0.1% in the Mennonite population (3% incidence of specific splice-site mutation in the liver phosphorylase gene of this religious group).

Autosomal recessive (classic form; accounts for about 25% of cases) and X-linked recessive form (phosphorylase kinase deficiency). Phosphorylase b kinase genes are multimeric (four different subunits, each coded by a unique gene located on different chromosomes). Different isoforms of each enzyme with differential tissue expression exist.

Deficiency of liver phosphorylase, the ratelimiting enzyme of glycogenolysis, is activated by an enzyme cascade by a succession of enzymes resulting in insufficient liberation of glucose from the glycogen molecule. Neoglycogenesis is not affected. Even though the enzyme deficiency is usually incomplete, mild fasting hypoglycemia and associated hyperketosis with ketonuria are frequent.

Enzyme deficiency demonstrated on liver biopsy. Associated biologic disorders include mild hyperlipidemia, hypercholesterolemia, and, to a lesser extent, hypertriglyceridemia. Elevated serum transaminases with no other evidence of liver dysfunction is frequent. Molecular diagnostic testing is used to identify carriers and affected children.

Typically, symptomatology becomes apparent in children at the age of 1 to 5 years, who present with a protuberant abdomen, growth and mild motor retardation, mild fasting hypoglycemia, and hypotonia. Some patients are asymptomatic, but physical abdominal examination reveals hepatomegaly, which may be massive. Severe hypoglycemia is rare. Mild cardiomyopathy may occur in some patients.

Check blood glucose level, liver function and cardiac function. Assess degree of hypotonia.

Anesthetic management in this condition has not been described, but no particular problems would be predicted except for the potential for severe hypotonia. Dextrose-containing fluid may be used in patients at risk for hypoglycemia. If hypotonia is present, neuromuscular blocking agents should be titrated to effect (nerve stimulator) and depending on the planned procedure, postoperative mechanical ventilation may be required.

No agents specifically contraindicated. Cis-atracurium should be preferred in patients with altered liver function.

Other glycogen storage diseases.