Muscle phosphoglycerate mutase deficiency revisited
Ali Naini1, Antonio Toscano, Olimpia Musumeci
1Department of Neurology, Columbia University Medical Center, New York, New York, USA.
Archives of Neurology
|March 11, 2009
Summary
Glycogen storage disease type X, previously thought to affect primarily African Americans, occurs in diverse populations. Novel mutations in the PGAM2 gene cause this condition, often linked to muscle issues and sarcoplasmic reticulum proliferation.
Area of Science:
- Biochemistry
- Genetics
- Muscle Physiology
Background:
- Phosphoglycerate mutase (PGAM) deficiency, or glycogen storage disease type X, is a rare metabolic disorder.
- Historically, reported cases have predominantly been in individuals of African American descent.
Observation:
- This study details two patients of Pakistani and Italian ethnicity presenting with classic clinical and biochemical signs of glycogen storage disease type X.
- Both patients experienced exercise-induced muscle symptoms, including cramps and myalgia, with one also exhibiting myoglobinuria.
Findings:
- Molecular analysis identified two novel homozygous mutations in the PGAM2 gene, responsible for encoding the muscle subunit of PGAM.
- Muscle pathology revealed mild glycogen accumulation alongside significant tubular aggregates, indicative of sarcoplasmic reticulum proliferation.
- Biochemical assays confirmed severe, isolated PGAM deficiency in both individuals.
Implications:
- Glycogen storage disease type X is not exclusive to African Americans, highlighting the need for broader diagnostic considerations.
- The findings suggest genetic heterogeneity within PGAM deficiency and a potential association with sarcoplasmic reticulum abnormalities.
- This research expands the understanding of PGAM deficiency's genetic basis and clinical spectrum.
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