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Purine nucleotides important for normal cellular metabolism are derived endogenously from de novo synthesis and also from recycling of pre-formed purines via the so-called salvage pathway (Figure 1). The latter pathway contains a number of enzymes, the absence of which can lead to disturbances of purine metabolism and also severe clinical symptoms1. An example is the deficiency of the salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) which can lead either to the Lesch-Nyhan syndrome or X-linked gout1.

Adenine (APRT) and hypoxanthine-guanine (HGPRT) phosphoribosyltransferase deficiency were originally identified in children.1,2 The spectrum of manifestations in both is broad with similarities, but also important differences. Both are asociated with urinary calculi and can cause severe renal damage.1,2 Severe neurological problems are also found in complete HGPRT deficiency 1 but have not been noted in APRT deficiency. We have investigated 2 children presenting in renal failure that emphasise the problems of diagnosis and treatment of these 2 deficiencies and the particular difficulties encountered in the presence of impaired renal function.

The identification of 2,8-dihydroxyadenine (2,8-DHA), a uric acid analogue characterised by its extreme insolubility, as the principal component of so-called ‘uric acid’ stones in a young male child, was originally reported independently by workers in Paris and London1,2. The correct diagnosis resulted from the finding of nearly undetectable levels of the enzyme adenine phosphoribosyltransferase (APRT: EC 2.4.2.7) in erythrocyte lysates in the first instance1 and the detection of abnormal urinary levels of adenine (excreted together with 8, and 2, 8-DHA in consequence of the enzyme defect) in the latter case2. Since that time a further three cases have been identified in London2,3,4 (Dillon et al — in preparation). Another two are added to the list1,5 in this symposium by the French workers, one of which has appeared in abstract6 (Table 1).