Triosephosphate isomerase (TPI, EC 5.3.1.1) is an ubiquitously expressed enzyme that catalyses the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate in the energy-generating glycolytic pathway. Inherited defects in the TPI gene are characterised biochemically by markedly reduced TPI enzyme activity in all tissues resulting in metabolic block in glycolysis, with accumulating DHAP particularly in red cells. Clinical TPI deficiency is a rare autosomal recessive multi-system disorder characterised by non-spherocytic haemolytic anaemia, recurrent infections, cardiomyopathy, severe and fatal neuromuscular dysfunctions. Reviews of current literature show that after 30 years since TPI deficiency was first described, the disease still remains without effective therapy. However, several potential therapeutic strategies exist for the treatment of inherited metabolic disorders such as TPI deficiency. Development of an effective therapy for TPI deficiency presents a fascinating and formidable challenge for basic laboratory and clinical research. The major aim of this overview is to discuss the current knowledge of TPI deficiency with special emphasis on research efforts directed towards reversing the metabolic effects of the disorder.

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