COMPLETE DEFICIENCY OF ADENINE PHOSPHORIBOSYLTRANSFERASE - 3RD CASE PRESENTING AS RENAL STONES IN A YOUNG-CHILD

Many urinary stones or crystals identified in children result from the overexcretion of normally minor urinary constituents, compounds of limited solubility whose overexcretion may be the direct consequence of a block in an essential step in a metabolic pathway. Examples are found in hereditary oroticaciduria, xanthinuria and the Lesch-Nyhan syndrome. In the Lesch-Nyhan syndrome uric acid stones or gravel form because of gross overproduction of uric acid arising from a lack of the hypoxanthine salvage enzyme-hypoxanthine-guanine phosphoribosyltransferase (HGPRT: EC 2.4.2.8). These children also have bizarre neurological complications and other clinical manifestations. A complete lack of the other purine salvage enzyme, adenine phosphoribosyltransferase (APRT: EC 2.4.2.7), was described in children of two separate families, one in France and the other from the authors' own unit. Children with this deficiency also present with urolithiasis, because of the excretion of 2, 8-dihydroxyadenine, an extremely insoluble analogue of uric acid. The excretion of this compound follows the accumulation of adenine in the absence of the salvage enzyme, APRT, and its oxidation by xanthine oxidase via the 8-hydroxy intermediate. The authors report a third case of 2, 8-dihydroxyadenine stones in a child with a complete lack of the adenine salvage enzyme - adenine phosphoribosyltransferase (APRT). The propositus, a 20-mth-old girl of consanguineous Arab parents, presented with multiple urinary tract infections and supposed 'uric acid' stones in the right renal pelvis and left ureter. Both parents and one brother were heterozygotes for the defect, in keeping with an autosomal recessive mode of inheritance. In contrast with the other purine salvage enzyme disorder of childhood with true uric acid stones (the Lesch-Nyhan syndrome), uric acid excretion was normal in all family members. As in the authors' previous case, treatment with allopurinol, without alkali, has eliminated the urinary excretion of 2, 8-dihydroxyadenine: the stones were removed surgically. 2, 8-Dihydroxyadenine should be considered in any child thought to have uric acid stones and tests made to distinguish the two compounds.