Myopathic form of phosphoglycerate kinase (PGK) deficiency: a new case and pathogenic considerations.

We describe an 18-year-old man with muscle cramps and recurrent exertional myoglobinuria, without hemolytic anemia or brain dysfunction. Phosphoglycerate kinase (PGK) deficiency was documented in muscle and erythrocytes and molecular analysis of the PGK1 gene identified a novel mutation, T378P. This is the ninth case presenting with isolated myopathy, whereas most other patients show hereditary non-spherocytic hemolytic anemia alone or associated with brain dysfunction, and a few patients have myopathy plus brain involvement. Although the diverse tissue involvement in PGK deficiency remains unclear, all mutations in myopathic patients tend to cluster in the C terminal domain, adjacent to the substrate-binding pocket. This may lead to a failure in the closure of the N terminal and C terminal domains and loss of stability due to lack of inter-domain communication during the catalytic process.