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glycogen storage disease type 9a

MIM.306000 Xp22.2-p22.1

Friday 7 May 2010

Glycogen storage disease type IX is a metabolic disorder resulting from a deficiency of hepatic phosphorylase kinase, a hexadecameric enzyme comprising 4 copies each of 4 unique subunits encoded by 4 different genes:
- alpha (PHKA2)
- beta (PHKB; MIM.172490)
- gamma (PHKG2; 172471)
- delta (CALM1; 114180).

Mutations within the PHKA2, PHKB, and PHKG2 genes result in GSD9a, GSD9b (MIM.261750), and GSD9c (MIM.613027), respectively.

GSD9a is an X-linked recessive disorder, whereas the others are autosomal recessive.

Glycogen storage disease type IXa (GSD9a) is caused by mutation in the gene encoding the alpha-2 subunit of hepatic phosphorylase kinase (PHKA2; MIM.300798).

X-linked muscle PHK deficiency (GSD9D; MIM.300559) is caused by mutation in the gene encoding the muscle-specific alpha PHK subunit (PHKA1; MIM.311870).

GSD IXa has been further divided into types IXa1 (GSD9A1), with no PHK activity in liver or erythrocytes, and IXa2 (GSD9A2), with no PHK in liver, but normal activity in erythrocytes.

The clinical presentation of both subtypes is the same, and both are caused by mutations in the PHKA2 gene.

However, mutations that result in IXa2 are either missense or small in-frame deletions or insertions enabling residual enzyme expression in erythrocytes.