The feasibility of replacement therapy for inherited disorder of glycolysis: Triosephosphate isomerase deficiency (Review)

Triosephosphate isomerase (TPI, EC 5.3.1.1) is an ubiquitously expressed en zyme that catalyses the interconversion of dihydroxyacetone phosphate (DHAP ) and glyceraldehyde-3-phosphate in the energy-generating glycolytic pathwa y. Inherited defects in the TPI gene are characterised biochemically by mar kedly reduced TPI enzyme activity in all tissues resulting in metabolic blo ck in glycolysis, with accumulating DHAP particularly in red cells. Clinica l TPI deficiency is a rare autosomal recessive multi-system disorder charac terised by non-spherocytic haemolytic anaemia, recurrent infections, cardio myopathy, severe and fatal neuromuscular dysfunctions. Reviews of current l iterature show that after 30 years since TPI deficiency was first described , the disease still remains without effective therapy. However, several pot ential therapeutic strategies exist for the treatment of inherited metaboli c disorders such as TPI deficiency. Development of an effective therapy for TPI deficiency presents a fascinating and formidable challenge for basic l aboratory and clinical research. The major aim of this overview is to discu ss the current knowledge of TPI deficiency with special emphasis on researc h efforts directed towards reversing the metabolic effects of the disorder.