J Med Genet 37:376-377 doi:10.1136/jmg.37.5.376
  • Letters to the editor

Phosphorylase kinase deficient liver glycogenosis: progression to cirrhosis in infancy associated with PHKG2 mutations (H144Y and L225R)

  1. * Institut für Physiologische Chemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany
  2. The Sheffield Children's Hospital, University of Sheffield, Division of Child Health, Sheffield S10 2TH, UK
  1. Dr Kilimann,manfred.kilimann{at}

    Editor—Deficiency of phosphorylase kinase (Phk), a regulatory protein kinase in glycogen metabolism, is the most frequent cause of hepatic glycogen storage disease (GSD). Patients typically present as infants with hepatomegaly, growth retardation, and raised triglycerides, cholesterol, and transaminases. Compared to other types of liver GSD, the condition is usually mild and its course is benign such that patients may even become asymptomatic as they grow up. Hypoglycaemia and lactic acidosis, for example, are uncommon in Phk deficiency in contrast to glucose-6-phosphatase deficiency (GSD type I). Hepatic architecture typically remains normal, unlike GSD III (debranching enzyme deficiency) in which hepatic fibrosis is common, and unlike GSD IV (branching enzyme deficiency) which usually progresses to cirrhosis in infancy. Only two infants with Phk deficiency and cirrhosis have been reported. Development of fibrosis and even cirrhosis was found in five older Japanese patients, but it remains to be clarified whether this observation can be generalised and also applies to other ethnic groups.1-5

    Phk is a complex enzyme consisting of four different subunits, (αβγδ)4, and isoforms or splice variants exist for each subunit. This gives rise to genetic and phenotypic heterogeneity of Phk deficiency.6 A muscle specific form of Phk deficiency is caused by mutations in the gene for the muscle isoform of the α subunit, PHKA1, which resides on the long arm of the X chromosome, whereas liver Phk deficiency can be caused by mutations in three genes: PHKA2 …