Glycogen storage disease (GSD) due to phosphorylase kinase deficiency is a group of inborn errors of glycogen metabolism that is clinically and genetically heterogeneous. This group comprises GSD due to liver phosphorylase kinase (PhK) deficiency, GSD due to muscle PhK deficiency and GSD due to liver and muscle PhK deficiency (see these terms).
The prevalence at birth is estimated at around 1/100,000.
GSD due to liver PhK deficiency is the most common sub-type and presents in early childhood with hepatomegaly, growth retardation, and mild delay in motor development. During adulthood, symptoms usually disappear. Patients with GSD due to liver and muscle PhK deficiency may have marked hepatomegaly and mild muscular hypotonia in childhood. GSD due to muscle PhK deficiency presents in adolescence or adulthood with exercise intolerance, myalgia, and sometimes myoglobinuria but symptoms are generally mild.
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 PhK deficiency is due to mutations in the PHKA2 or PHKG2 genes encoding the liver isoforms of the alpha and gamma subunits of PhK. Transmission is X-linked and autosomal recessive, respectively. GSD due to liver and muscle PhK deficiency is transmitted in an autosomal recessive manner and is due to mutations in the PHKB gene which encodes the beta subunit of PhK. The muscle-specific isoforms of the alpha and gamma subunits of PhK are encoded by the PHKA1 and PHKG1 genes respectively, but until now mutations have only been found in the PHKA1 gene in patients with GSD due to muscle PhK deficiency. Transmission is X-linked.
Last update: May 2011
- Dr Roseline FROISSART
- Pr Philippe LABRUNE
- Dr Pascal LAFORET