Adenine phosphoribosyltransferase deficiency and 2,8-dihydroxyadeninuria.

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of purine metabolism causing 2,8-dihydroxyadenine urinary tract stones and crystal nephropathy. Disease manifestations include acute kidney injury (AKI), progressive chronic kidney disease (CKD), and not infrequently, kidney failure. A significant proportion of affected individuals remain asymptomatic into adulthood. The diagnosis of APRT deficiency should be considered in all children presenting with renal colic, radiolucent urinary stones and/or AKI, as well as in infants with a history of reddish-brown diaper stain. Indeed, the disorder should be considered in any person with radiolucent urinary stones and in young and middle-aged individuals with progressive CKD, particularly when a kidney biopsy reveals tubulointerstitial nephropathy of unknown cause. The presence of biallelic pathogenic APRT mutations identified through targeted multi-gene panels or single-gene testing confirms the diagnosis of APRT deficiency. As kidney stone analysis can be false-positive, this method can only be considered suggestive of APRT deficiency, and confirmatory testing must be carried out in all cases. Timely diagnosis and treatment with a xanthine oxidoreductase inhibitor, either allopurinol or febuxostat, have in several studies, based on different levels of evidence, been found to be both highly effective and safe in APRT deficiency. Appropriate pharmacotherapy significantly reduces kidney stone recurrence, slows CKD progression and appears to prevent the development of kidney failure. The outcome of kidney transplantation in individuals with APRT deficiency is comparable to those with other causes of kidney failure when allopurinol or febuxostat therapy is initiated before the transplant procedure.