Phosphoglycerate deficiency

Hereditary deficiency of phosphoglycerate kinase (PGK) is associated with hereditary hemolytic anemia and often with central nervous system dysfunction and/or myopathy. The first case, reported by Kraus et al. (K24), is a heterozygous female, and the results are not so clear. The second family, reported by Valentine et al. (V3), is a large Chinese family, whose pedigree study indicates that PGK deficiency is compatible with X-linked inheritance. To date, 22 families have been reported (04, T25, Y3). Nine of these have manifested both symptoms five have shown only hemolysis seven have shown the central nervous system dysfunction and/or myopathy but without hemolysis and one case, PGK Munchen, is without clinical symptoms (F5). PGK II is an electrophoretic variant found in New Guinea populations (Y2). Red blood cell enzyme activity, specific activity, and the kinetic properties of this polymorphic variant are normal. 

F5. Fujii, H., Krietsch, W. K. G., and Yoshida, A., A single amino acid substitution (Asp -> Asn) in a phosphoglycerate kinase variant (PGK Miinchen) associated with enzyme deficiency. J. Biol. Chem. 255,6421-6423 (1980). 

T20. Toscano, A., Tsujino, S., Vita, G., Shanske, S., Messina, C., and DiMauro, S., Molecular basis of muscle phosphoglycerate mutase (PGAM-M) deficiency in the Italian kindred. Muscle Nerve 19, 1134-1137(1996). 

T24. Tsujino, S., Tonin, P Shanske, S., Nohria, V., Boustany, R.-M., Lewis, D Chen, Y.-T., and DiMauro, S., A splice junction mutation in a new myopathic variant of phosphoglycerate kinase deficiency (PGK North Carolina). Ann. Neurol. 35,349-353 (1994). 

Garson, O. M., Hereditary hemolytic anemia associated with phosphoglycerate kinase deficiency in erythrocytes and leukocytes. New Engl. J. Med. 280,528-534 (1969). 

Phosphoglycerate kinase deficiency is an X-linked recessive disease (type IX, Fig. 42-1). The most common clinical presentation includes hemolytic anemia with or without CNS involvement (see below). Thus far, ten patients have been described with a purely myopathic... 

Phosphoglycerate mutase deficiency is an autosomal recessive myopathy caused by a genetic defect of the muscle subunit of the enzyme PGM (type X, Fig. 42-1). 12 patients with this enzyme deficiency have been identified thus far. 

A different problem results from deficiency of enzymes of glycolysis such as phosphofructokinase (see Box 20-D), phosphoglycerate rnutase, and pyruvate kinase. Lack of one isoenzyme of phosphoglycerate rnutase in muscle leads to intolerance to strenuous exercise/ A deficiency in pyruvate kinase is one of the most common defects of glycolysis in erythrocytes and leads to a shortened erythrocyte lifetime and hereditary hemolytic anemia.s... 

Phosphoglycerate kinase deficiency, the seventh enzyme step of the glycolytic pathway, is an inherited X-linked recessive disorder, meaning it mostly affects males, although females are carriers. Onset is infancy to early adulthood. Symptoms may include anaemia, enlargement of the spleen, mental retardation and epilepsy (seizures) more rarely, weakness, exercise intolerance, muscle cramps and episodes of myoglobinuria occur. 

Phosphoglycerate mutase deficiency, the eighth enzyme step of glycolysis, is inherited autosomal recessive. Onset occurs in childhood to early adulthood. Symptoms include exercise intolerance, cramps, muscle pain and sometimes myoglobinuria. 

Fujii H, Miwa S. Other erythrocyte enzyme deficiencies associated with non-haematological symptoms phosphoglycerate kinase and phosphofructokinase deficiency. Baillieres Best Pract Res Clin Haematol 2000 13 141-8. 

Phosphoglycerate kinase deficiency is a sex-finked genetic disorder (located on the X chromosome). As a result, far more males than females suffer from this disease. There are many cfinical features associated with this deficiency, although only rarely are they all found in the same patient. These symptoms range from mental retardation and seizures to a slowly progressive myopathy. 

Phosphoglycerate mutase deficiency has been mapped on chromosome 7. The disorder is found predominantly in U.S. African American, Italian, and Japanese families. The cfinical features include exercise intolerance, muscle pain, and myoglobinuria following more intense exercise. 

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