Glycogenosis type VIII

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Background     Reference

BACKGROUND AND CLINICAL INFORMATION: Head  

Summary of glycogenosis     Classificaiton of glycogenoses by enzyme deficiency

Summary: Glycogenosis type VIII is resulted from deficiency of phosphorylase b-kinase, the enzymes that convert inactive phosphorylase b form into the active a form. Several clinical isoforms are present. Aside from the severe form that involves the heart, the other forms are compatible with prolonged survival.

Biochemistry: Phosphorylase b-kinase activates the phosphorylase from its inactive b form into the active a form. It is a tetrameric enzyme (a-, b-, g-, and d-subunits). The a-subunit has two isoforms one for the muscle and one for the liver, and are coded by two separate genes on the X-chromosome. The muscle isoform is coded for on chromosome Xq12-q13. The b- and g-subunits are coded for on chromosome 16q12-q13 and 17. Tissue specificity is often resulted from variation of the g-subunit.

·         a- and b-subunit: regulatory

·         g-subunit: catalytic

·         d-subunit: this is a calmodulin

Genetics: It is not very clear. An X-linked recessive form that affects only the liver has been documented. However, an autosomal recessive form that involves both the phosphorylase in liver and muscle has also been reported.

Clinical variants:

·         Most common X-linked recessive form: This form affects the liver only. Some of the cases may be autosomal recessive.

·         Liver and muscle form: This is autosomal recessive. The hepatomegaly may resolve with age and the myopathy is non-progressive.

·         Muscle form: Most cases have childhood onset exercise intolerance although cases that presented with infantile weakness have also been reported.

·         Cardiac form: The index cases have infantile cardiomyopathy and died within 6 months. Phosphorylase activity in liver and muscle is normal (Mizuta K et al., 1984; Servidei S et al., 1986)

REFERENCES: Head

Van den Berg IE, Berger R. Phosphorylase b kinase deficiency in man: a review. J Inherit Metab Dis. 1990;13(4):442-51. Review.

Mizuta K, Hashimoto E, Tsutou A, Eishi Y, Takemura T, Narisawa K, Yamamura H. A new type of glycogen storage disease caused by deficiency of cardiac phosphorylase kinase. Biochem Biophys Res Commun. 1984 Mar 15;119(2):582-7.