Glucose-6-phosphate isomerase deficiency

Baillieres Best Pract Res Clin Haematol. 2000 Mar;13(1):89-101. doi: 10.1053/beha.1999.0059.

Abstract

Most of the metabolic needs of erythrocytes are covered by glycolysis, the oxidative pentose phosphate pathway and the glutathione cycle. Hereditary enzyme deficiencies of all these pathways have been identified, among which glucose-6-phosphate isomerase (GPI) deficiency is the second most frequent erythroenzymopathy in glycolysis, being associated with non-spherocytic haemolytic anaemia of variable severity. This autosomal recessive genetic disorder may be associated in some cases with neurological impairment. GPI is a dimeric enzyme that catalyses the reversible interconversion of fructose-6-phosphate and glucose-6-phosphate. Virtually all the mutant gene products reported are characterized by marked instability and normal substrate affinities, but altered catalytic activity and electrophoretic migration rates. At the nucleotide level, 29 mutations have been reported. This chapter reviews (a) the clinical pattern of the condition; (b) biochemical and molecular studies; (c) structure-function relationships; (d) the molecular basis of neurological dysfunctions sometimes associated with GPI deficiency; and (e) the correlation between the severity of the anaemia and the molecular defect.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Hemolytic, Congenital Nonspherocytic* / enzymology
  • Anemia, Hemolytic, Congenital Nonspherocytic* / genetics
  • Anemia, Hemolytic, Congenital Nonspherocytic* / therapy
  • Erythrocytes / enzymology
  • Glucose-6-Phosphate Isomerase / blood
  • Glucose-6-Phosphate Isomerase / chemistry
  • Glucose-6-Phosphate Isomerase / genetics
  • Glycolysis
  • Humans
  • Mutation
  • Nervous System Diseases / enzymology
  • Nervous System Diseases / genetics
  • Structure-Activity Relationship

Substances

  • Glucose-6-Phosphate Isomerase