Adenine phosphoribosyltransferase (APRT) deficiency: an increasingly recognized disease

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder which causes high urinary 2,8-dihydroxyadenine (2,8-DHA) excretion, resulting in urolithiasis and crystal nephropathy. It is caused by mutations in the APRT gene. Even though it is an inherited kidney stone disease, the varied clinical presentations, even within a family with the same underlying genetic variants, can lead to delayed diagnosis with some only being recognized in adulthood and even, following a kidney transplant. First presentations include symptoms of reddish-brown diaper stains, urinary tract infections, urolithiasis, acute kidney injury from obstructive uropathy and/or intratubular 2,8-DHA crystallization or kidney failure. Siblings of index cases should be screened for APRT deficiency. An early diagnosis and treatment with xanthine oxidoreductase inhibitors (XORi) can preserve kidney function and/or prevent progressive kidney injury and kidney failure. In this review, we will discuss the pathophysiology, clinical presentations, investigations, and management of APRT deficiency.