Complete deficiency of adenine phosphoribosyltransferase: a third case presenting as renal stones in a young child.

Abstract

SUMMARYWe 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-month-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 our 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.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.

Dihydroxyadenine Urolithiasis in Children with Partial Deficiency of Adenine Phosphoribosyltransferase

“…Thus, the prevention of dihydroxyadenine formation is most important in these pa tients. Allopurinol, a xanthine oxydase inhib itor, can prevent dihydroxyadenine forma tion, but its effect may be considerably vari able from patient to patient as indicated by Rarratt et al [4], Our experience in 2 cases has agreed with their opinion. Therefore, if possible, appropriate dosage of allopurinol should be determined to control the excretion of dihydroxyadenine in the urine.…”

“…Because dihy droxyadenine is an extremely insoluble com pound, the patients with this deficiency present with urolithiasis. Since the first re port by Cartier and co-workers [1,2], 3 addi tional cases from different families have been demonstrated in the literature [3][4][5].…”

“…Since 2,8-dihydroxyadenine urolithiasis due to complete deficiency of adenine phos phoribosyltransferase (APRT), which is a pu rine salvage enzyme, was first found by Cartier and co-workers [ 1,2], 4 cases have been reported in the literature [3][4][5], Kuroda et al [6] described that urinary calculi composed of dihydroxyadenine are formed even in par tial deficiency of this enzyme. Subsequently, Takeuchi et al [7] reported a similar case.…”

Adenine phosphoribosyltransferase deficiency in children

“…A timely diagnosis of APRT deficiency is crucial since early treatment with allopurinol can prevent further nephrolithiasis and may stabilize or even improve renal function [7,8]. Given the rarity of the disease, only a few reports limited to single cases presenting the clinical and biological data of APRT deficiency in children are available, especially in the Caucasian population [8][9][10][11]. Long-term data on treatment outcome are scarce.…”

Adenine Phosphoribosyltransferase Deficiency

“…This technique does not detect any enzyme activity in individuals with type I APRT deficiency. Type I deficiency mainly affects white individuals but has been also reported in people originating from countries worldwide (6,7,15). In type II deficiency, which accounts for most cases in Japan (4), APRT has a reduced affinity for the cosubstrate 5-phosphoribosyl-1-pyrophosphate and the enzyme activity in cell lysates is about 25% of normal values (16).…”