Clinical features and genotype of adenine phosphoribosyltransferase deficiency in Iceland

The purpose of this study was to characterize the clinical, diagnostic, and prognostic features of adenine phosphoribosyltransferase (APRT) deficiency in Icelandic patients, as well as determine their genotype. Medical record s of all known patients in Iceland were reviewed. Urinalysis and polymerase chain reaction-based DNA mutation analysis were performed in all patients, siblings, and living parents of index cases. Twenty-three individuals homo zygous for type I APRT deficiency were identified in 16 families from 1983 to 1998. There were 12 males and 11 females, and the median age at diagnosi s was 37 years (range, 0.5 to 62 years). Seventeen patients were index case s and 6 patients were diagnosed during screening of first-degree relatives. Eighteen patients had symptomatic disease, 15 of whom experienced nephroli thiasis; 4 patients had mild to moderate renal insufficiency, 1 patient had advanced renal failure, and 1 patient died of uremic complications. Six pa tients experienced recurrent urinary tract infections and 3 infants had a h istory of reddish-brown diaper stains. Five patients were asymptomatic; 3 o f these patients were diagnosed during routine urinalysis and 2 patients we re identified during family screening. Urinary 2,8-dihydroxyadenine crystal s were detected in all cases, except for the patient who died of end-stage renal failure. All 23 patients were homozygous for the same mutation (D65V) in the APRT gene. Allopurinol therapy successfully prevented further stone formation and significantly improved renal function in most patients with renal insufficiency. Our results suggest that APRT deficiency may be more c ommon than previously recognized and can lead to severe renal failure if le ft untreated. (C) 2001 by the National Kidney Foundation, Inc.