Glycogen Storage Disease Type VII (Tarui Disease) via the PFKM Gene

Glycogen storage disease type VII (GSDVII; OMIM 232800), also known as Tarui disease, is a rare childhood-onset disorder. The most consistent feature is exercise intolerance accompanied by muscle pain, cramps, and nausea. Intense exercise may induce myoglobinuria and even kidney failure. Other symptoms may include jaundice, gallstones, and gout. Adult and elderly patients may experience progressive muscle weakness. Symptoms are generally similar to glycogen storage disease type V. A less common, rapidly progressive and fatal infantile form characterized by myopathy, blindness, and seizures has been reported.

GSDVII is an autosomal recessive disorder caused by absence or substantial reduction in the activity of the muscle form of the glycolysis enzyme phosphofructokinase. Muscle phosphofructokinase is encoded by the PFKM gene on chromosome 12. Different and distinct genes (PFKL and PFKP) encode the liver and platelet forms of the enzyme. About 20 different causative variants have been reported in PFKM (www.hgmd.org; Rabin and Sherman. Hum Mut 6:1-6, 1995). These variants are predominantly missense and splicing and are located throughout the length of the gene. Two founder variants account for ~95% of the known variants in Ashkenazi Jewish patients.

Unknown. Because so few causative variants have been reported in the literature, the frequency of uninterpretable variants may be somewhat higher than in other sequencing tests.

This test provides full coverage of all coding exons of the PFKM gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.