Title: 142 FURTHER EVIDENCE FOR A ‘NEW’ PURINE DEFECT, INOSINE TRIPHOSPHATE (ITP) PYROPHOSPHOHYDROLASE DEFICIENCY
Abstract: Raised levels of an unusual nucleotide were found in the erythrocytes of 3 members of a consanguinous kindred in which the propositus presented with immunodeficiency due to ADA deficiency. 3 siblings, the parents and 7 of 9 relatives were heterozygotes. This nucleotide and a corresponding diphosphate, were identified as ITP (mean 157μmol/l) and IDP (mean 28μmol/l) by their HPLC characteristics pre/post degradation. They have not been seen in 1000 other subjects. ITP formation from radiolabelled precursors was also investigated. The 3 subjects with raised ITP levels accumulated up to 50% of the counts in ITP/IDP, 7 of 8 other family members had a mean of 21%. Only 6% of control erythrocytes showed any such incorporation (11-25%). These results accord with those of vanderheiden (Nature 1967;216:1036-7) who found high erythrocyte ITP levels in 7 of 6000 persons studied, 2 of whom were siblings. Henderson et al (Can J Biochem 1977;55:359-64) also showed that erythrocytes of 5% of controls accumulated relatively high amounts of ITP from radiolabelled precursors. This was ascribed to a deficiency of a specific ITP pyrophosphohydrolase IEC 3.6.1.19:ITPase) which followed a co-dominant pattern and suggested a cycle in which ITP was continuously synthesised and degraded. The finding of this defect in a large kindred provides a unique opportunity to investigate the inheritance of ITPase deficiency and the activity of the putative ‘inosinate cycle’, as well as the clinical significance of ITP accumulation, in more detail.