The molecular genetic basis of muscle phosphoglycerate mutase (PGAM) deficiency

Area of Science:

• Biochemistry
• Genetics
• Human Physiology

Background:

• Phosphoglycerate mutase (PGAM) is a key glycolytic enzyme.
• The MM isoenzyme, PGAM-M, is predominant in human skeletal muscle.
• PGAM-M deficiency is a rare condition linked to exercise intolerance.

Observation:

• Five patients with PGAM-M deficiency were studied, including four African-Americans and one Caucasian.
• Clinical presentation included exercise intolerance, muscle cramps, and myoglobinuria.
• Previous cases of PGAM-M deficiency were identified starting in 1981.

Findings:

• Three patients were homozygous for a G-to-A mutation at codon 78, resulting in a premature stop codon.
• A fourth patient was compound heterozygous for the codon 78 mutation and an A-to-C mutation at codon 89.
• The Caucasian patient was homozygous for a C-to-T mutation at codon 90, leading to an Arg-to-Trp substitution.

Implications:

• Identifies specific genetic mutations causing PGAM-M deficiency.
• Provides molecular basis for exercise intolerance in affected individuals.
• Contributes to understanding glycolytic enzyme disorders and their clinical manifestations.