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Glycogen storage disease due to liver phosphorylase kinase deficiency

Synonym(s) GSD due to liver phosphorylase kinase deficiency
GSD type 9A
GSD type 9C
GSD type IXa
GSD type IXc
Glycogen storage disease type 9A
Glycogen storage disease type 9C
Glycogen storage disease type IXa
Glycogen storage disease type IXc
Glycogenosis due to liver phosphorylase kinase deficiency
Glycogenosis type 9A
Glycogenosis type 9C
Glycogenosis type IXa
Glycogenosis type IXc
Prevalence Unknown
Inheritance Autosomal recessive
or X-linked recessive
Age of onset Childhood
  • E74.0
MeSH -
MedDRA -


Disease definition

Glycogen storage disease (GSD) due to liver phosphorylase kinase (PhK) deficiency is a benign inborn error of glycogen metabolism characterized by hepatomegaly, growth retardation, and mild delay in motor development during childhood.


It is the most common presentation of glycogen storage disease due to PhK deficiency (see this term) with an incidence estimated at less than 1/100,000 births.

Clinical description

Patients usually present in early childhood with hepatomegaly, growth retardation, and mild delay in motor development. Fast-induced hypoglycemia and hyperlipidemia are variable and, if present, are generally mild. Adults are generally asymptomatic. Full-cheeked round face and osteopenia have been reported on exceptional occasions in cases with an X-linked inheritance. An increased risk of cirrhosis due to liver fibrosis is observed in cases with autosomal recessive inheritance.


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 calmodulin) encoded by different genes on different chromosomes and differentially expressed in various tissues. The most frequent type of GSD due to liver PhK deficiency is the X-linked recessive (XLG) type that is due to mutations in the PHKA2 gene (Xp22.2-p22.1) encoding the liver isoform of the alpha-subunit. When the enzymatic deficiency is found both in erythrocytes and liver cells, the disorder is classified as XLG1, whereas when the deficiency can only be demonstrated in liver cells, it is classified as XLG2, although studies have shown that, in both cases, mutations occur within the same subunit. The autosomal recessive type is due to mutations in the PHKG2 gene (16p12.1-p11.2) encoding the liver isoform of the gamma-subunit. PhK deficiency due to all these mutations leads to glycogen accumulation in the liver.

Diagnostic methods

Biochemical diagnosis is made by measuring phosphorylase kinase activity in blood cells or in a liver biopsy. Some patients may have normal activity in red blood cells (XLG2 variant). Serum transaminase levels may 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 deficiency (GSD type I) (see these terms).

Management and treatment

Most patients require no specific treatment. Hypoglycemia can be controlled by adequate dietary treatment (frequent meals rich in carbohydrates, and supplements of uncooked starch).


The clinical course is benign with patients reaching their full height and weight during adulthood. Life expectancy is normal.

Expert reviewer(s)

  • Dr Roseline FROISSART
  • Pr Philippe LABRUNE

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