Phosphoglycerate mutase deficiency (glycogen storage disease X) caused by a novel variant in PGAM-M

Phosphoglycerate mutase enzyme deficiency in muscle causes a metabolic myopathy (glycogen storage disease X) characterized by exertional muscle contractures, weakness, hyperCKemia, and myoglobinuria. Six different autosomal recessive variants in PGAM-M have been described thus far (Salameh et al., 2013). In this case report, we report a novel disease-causing variant. A 52-year-old African-American woman presented with exertional muscle contractures, myalgias, and weakness since childhood including an episode of rhabdomyolysis. Neurologic examination and EMG were normal. CK was mildly elevated at rest and over 20,000 U/L during her episode of rhabdomyolysis. Muscle biopsy revealed subsarcolemmal collections suggestive of tubular aggregates. Phosphoglycerate mutase activity was 8% of the reference value. PGAM-M sequencing showed compound heterozygous variants: c.233G>A, which has been found only in African-Americans with this disease, and a novel variant, c.278G>A. This case expands the genetic spectrum of phosphoglycerate mutase deficiency.