ClinVar

In an 18-year-old man of Arab Bedouin descent with PGK1 deficiency (300653), Spiegel et al. (2009) identified a 1132A-C transversion in exon 10 of the PGK1 gene, resulting in a thr378-to-pro (T378P) substitution in a highly conserved residue. The patient had a myopathic phenotype, with onset of muscle cramps and exercise-induced pigmenturia at age 7 years. He had no evidence of hemolytic anemia or neurologic involvement; serum creatine kinase was increased. Protein structural analysis predicted that the mutation would destabilize an alpha-helix and interfere with the contact of domains responsible for proper catalytic interactions with nucleotide phosphates. Biochemical studies showed decreased PGK1 activity in muscle (0.9% of control values) and erythrocytes (1.6%). The patient's unaffected mother and 2 sisters were heterozygous for the mutation.