Glycogen Storage Disease Due To Liver And Muscle Phosphorylase Kinase Deficiency

A benign inborn error of glycogen metabolism. It is the mildest form of GSD due to PhK deficiency.

Epidemiology

Prevalence is unknown.

Clinical description

The disease manifests in childhood. Patients have marked hepatomegaly and mild muscular hypotonia. Hypoglycemia may occur only after prolonged fasting. These symptoms improve with age and adults are generally asymptomatic.

Etiology

Phosphorylase kinase (PhK) is an enzyme which plays a key role in the regulation of glycogenolysis as it is required for glycogen phosphorylase activation. It consists of four copies of each four subunits (alpha, beta, gamma and calmoduline) encoded by different genes on different chromosomes and differentially expressed in various tissues. GSD due to liver and muscle PhK deficiency is due to mutations in the PHKB gene (16q12-q13) which encodes the beta subunit.

Diagnostic methods

Biochemical diagnosis can be made by measuring phosphorylase kinase activity in blood cells or in a liver or muscle biopsy. Serum transaminase levels may also be elevated. Genetic testing is useful to confirm or establish the diagnosis.

Differential diagnosis

Differential diagnoses include other glycogen storage diseases such as GSD due to liver phosphorylase deficiency (GSD type VI), GSD due to glycogen debranching enzyme deficiency (GSD type III), and GSD due to glucose-6-phosphatase (GSD type I) (see these terms).

Genetic counseling

Transmission is autosomal recessive.

Management and treatment

Most patients do not require any specific treatment; a few patients may need to use cornstarch snacks.

Prognosis

Prognosis is good.