Alternative titles; symbols
SNOMEDCT: 61772003; ORPHA: 97234;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7p13 | Glycogen storage disease X | 261670 | Autosomal recessive | 3 | PGAM2 | 612931 |
A number sign (#) is used with this entry because glycogen storage disease X (GSD10) is caused by homozygous or compound heterozygous mutation in the PGAM2 gene (612931), which encodes muscle phosphoglycerate mutase, on chromosome 7p13.
DiMauro et al. (1981) studied a 52-year-old who had onset in adolescence of exercise-induced cramps, occasional myoglobinuria, and intolerance for strenuous exercise. However, he led a relatively normal life including service in the army. Physical examination showed gouty tophi and signs of severe coronary arteriosclerosis. Muscle phosphoglycerate mutase activity was 5 to 7% of the lowest control value.
Bresolin et al. (1983) reported a 17-year-old girl with recurrent myoglobinuria after intense exercise. Muscle biopsy showed increased PAS stain with twice normal glycogen concentration. PGAM2 activity was 6% of normal controls. Intermediate PGAM activities, 39% and 50%, respectively, were found in muscle biopsies from the patient's asymptomatic parents, indicating autosomal recessive inheritance.
Additional patients were reported by Kissel et al. (1985) and Vita et al. (1990).
Tsujino et al. (1993) reported a 17-year-old girl with GSD10 who complained of exercise intolerance since age 8 years; intense exertion caused pain and cramps in the exercising muscles. During episodes of myalgia, increases of serum creatine kinase were documented but there was no pigmenturia. A brother complained of similar exercise intolerance with cramps and had persistently elevated serum creatine kinase. Tsujino et al. (1993) also reported a 30-year-old African American man with GSD10 who was admitted to the hospital because of pigmenturia that appeared a few hours after he ran a race. Serum creatine kinase was greatly elevated and myoglobin was demonstrated in the urine. He developed renal failure that required hemodialysis. He had had 2 similar episodes, at ages 21 and 22 years, both after strenuous exercise.
Hadjigeorgiou et al. (1999) reported a Japanese family with GSD10 due to a G97D mutation (612931.0004) in the PGAM2 gene. Two family members heterozygous for the mutation presented with exercise intolerance and muscle cramps.
Autosomal recessive inheritance was supported by the finding of Bresolin et al. (1983) that muscle extracts from the unaffected parents of their patient exhibited approximately 50% of normal PGAM enzymatic activity.
In 5 patients with muscle phosphoglycerate mutase deficiency, Tsujino et al. (1993) identified 3 homozygous or compound heterozygous mutations in the PGAM2 gene (612931.0001-612931.0003). Four of the 5 patients were African American; the fifth was Italian.
Bresolin, N., Ro, Y.-I., Reyes, M., Miranda, A. F., DiMauro, S. Muscle phosphoglycerate mutase (PGAM) deficiency: a second case. Neurology 33: 1049-1053, 1983. [PubMed: 6308514] [Full Text: https://doi.org/10.1212/wnl.33.8.1049]
DiMauro, S., Miranda, A. F., Khan, S., Gitlin, K., Friedman, R. Human muscle phosphoglycerate mutase deficiency: newly discovered metabolic myopathy. Science 212: 1277-1279, 1981. [PubMed: 6262916] [Full Text: https://doi.org/10.1126/science.6262916]
DiMauro, S., Miranda, A. F., Olarte, M., Friedman, R., Hays, A. P. Muscle phosphoglycerate mutase deficiency. Neurology 32: 584-591, 1982. [PubMed: 6283419] [Full Text: https://doi.org/10.1212/wnl.32.6.584]
DiMauro, S., Miranda, A. F., Sakoda, S., Schon, E. A., Servidei, S., Shanske, S., Zeviani, M. Metabolic myopathies. Am. J. Med. Genet. 25: 635-651, 1986. [PubMed: 2878616] [Full Text: https://doi.org/10.1002/ajmg.1320250406]
Hadjigeorgiou, G. M., Kawashima, N., Bruno, C., Andreu, A. L., Sue, C. M., Rigden, D. J., Kawashima, A., Shanske, S., DiMauro, S. Manifesting heterozygotes in a Japanese family with a novel mutation in the muscle-specific phosphoglycerate mutase (PGAM-M) gene. Neuromusc. Disord. 9: 399-402, 1999. [PubMed: 10545043] [Full Text: https://doi.org/10.1016/s0960-8966(99)00039-5]
Kissel, J. T., Beam, W., Bresolin, N., Gibbons, G., DiMauro, S., Mendell, J. R. Physiologic assessment of phosphoglycerate mutase deficiency: incremental exercise tests. Neurology 35: 828-833, 1985. [PubMed: 2987758] [Full Text: https://doi.org/10.1212/wnl.35.6.828]
Tsujino, S., Sakoda, S., Mizuno, R., Kobayashi, T., Suzuki, T., Kishimoto, S., Shanske, S., DiMauro, S., Schon, E. A. Structure of the gene encoding the muscle-specific subunit of human phosphoglycerate mutase. J. Biol. Chem. 264: 15334-15337, 1989. [PubMed: 2549058]
Tsujino, S., Shanske, S., Sakoda, S., Fenichel, G., DiMauro, S. The molecular genetic basis of muscle phosphoglycerate mutase (PGAM) deficiency. Am. J. Hum. Genet. 52: 472-477, 1993. [PubMed: 8447317]
Vita, G., Toscano, A., Bresolin, N., Meola, G., Barbiroli, B., Baradello, A., Messina, C. Muscle phosphoglycerate mutase (PGAM) deficiency in the 1st Caucasian patient. (Abstract) Neurology 40: 296 only, 1990. [PubMed: 2300252] [Full Text: https://doi.org/10.1212/wnl.40.2.296]