Unstable triosephosphate isomerase (TPI)

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This study was undertaken in the investigation of a child with chronic non-spherocytic haemolytic anaemia. B.C. was born in 1977 of unrelated parents. His father has β-thalassaemia minor. He required an exchange transfusion for neonatal jaundice and subsequently has had persistent anaemia, splenomegaly and intermittent jaundice. Delayed gross motor development was noted at 6 mth of age, and increasing spasticity from 14 mth. Haemoglobin electrophoresis and globin chain synthesis studies established that B.C. also had thalassaemia minor. Microassays of 23 enzymes of the glycolytic and pentose phosphate pathways, and some enzymes and metabolites involved in glutathione metabolism were undertaken. Since his red cell population was invariably young, it was anticipated that increased activity of many enzymes known to be increased in reticulocyte-rich blood would be detected. This was found to be so, with the exception of TPI which was present at normal to low levels. This enzyme was shown to be unstable when haemolysate was stored on ice for 1 h (activity fell from 1973 I.U./g Hb to zero, control 3695 to 3096 I.U./g Hb) and when whole red cells were stored at –20°C (B.C. 1937 to 64 I.U/g Hb, control 3695 to 3068 I.U./g Hb). However, these phenomena did not clearly distinguish between the homozygous individual and presumed heterozygotes in a family study. Heat inactivation studies showed a clearer distinction, allowing for the possibility of antenatal diagnosis of this defect. Methods have been established for measurement of TPI in cultured foetal fibroblasts, and it is now planned to examine cultured fibroblasts from B.C. and his parents. The problems of identification of a TPI deficiency variant and the association with thalassaemia minor are discussed.