Glycogen Storage Disease Type X via the PGAM2 Gene

Glycogen storage disease type X (GSD10), also known as phosphoglycerate mutase (PGAM) deficiency, is a rare glycogen storage disease caused by deficiency of the muscle-specific isoform of PGAM (Tsujino et al. 1993). Most patients with GSD10 are asymptomatic in the absence of strenuous exercise, but experience exercise-induced myalgia, muscle-cramps, and myoglobinuria (Tsujino et al. 1993; Joshi et al. 2009; Naini et al. 2009; Tonin et al. 2009; Salameh et al. 2013). Some patients have also been reported to have tubular aggregates observed on muscle biopsy (Oh et al. 2006; Joshi et al. 2009; Naini et al. 2009; Salameh et al. 2013). To date, less than 20 patients with GSD10 have been reported worldwide (Tsujino et al. 1993; Oh et al. 2006; Joshi et al, 2009; Naini et al, 2009; Tonin et al. 2009; Salameh et al. 2013). Although the disorder appears to be more prevalent in individuals of African-American origin (Tonin et al. 2009), it has also been described in individuals of Italian, German, Pakistani, and Panamanian origin (Tsujino et al. 1993; Joshi et al. 2009; Naini et al. 2009; Salameh et al. 2013).

GSD10 is inherited in an autosomal recessive manner and is caused by variants in the PGAM2 gene. PGAM2 encodes the muscle subunit of phosphoglycerate mutase (PGAM). PGAM is a glycolytic enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate (Tsujino et al. 1993; Naini et al. 2009). To date, a total of about 10 pathogenic variants have been reported in PGAM2 associated with PGAM deficiency, including five missense, two nonsense, and one single nucleotide deletion (Human Gene Mutation Database). The most common variant reported to date is c.233G>A (p.Trp78*), which has been reported in all patients of African American origin (Salameh et al. 2013). 

Pathogenic PGAM2 variants were reported in 27/28 (96.4%) of alleles in 14 patients diagnosed with GSD10 (Salameh et al. 2013).

This test provides full coverage of all coding exons of the PGAM2 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).