Long-Term Outcomes of APRT Deficiency in Japanese

Adenine phosphoribosyltransferase (APRT) deficiency is an autosomal recessive purine metabolism disorder causing urolithiasis and CKD. It is classified as type I (complete deficiency) or type II (partial deficiency). Type II, linked to the APRT*J allele, has been reported only in Japanese patients. However, no study has examined genotype differences or long-term outcomes in this population. To address this, we conducted a literature review to clarify the clinical features and prognosis of Japanese patients with APRT deficiency.

A comprehensive search using PubMed and Ichushi-Web identified original articles in English or Japanese on Japanese patients with APRT deficiency with available full texts. Duplicates and reviews without patient data were excluded.

A total of 77 articles were identified through PubMed and 46 through Ichushi-Web. After screening reference lists, 25 publications comprising 28 cases (including 2 sibling cases) were selected. Including one additional case from our own institution, clinical information was collected from a total of 29 cases. Among the 29 cases, 17 (59%) were male, and the median age at diagnosis was 14 years, with 13 cases diagnosed in adulthood. The median follow-up duration was 2.5 years, and 18 cases (62%) had follow-up periods of at least one year. A history of urolithiasis or brownish diaper staining, characteristic findings of APRT deficiency, was observed in 14 cases (31%). Regarding the mode of diagnosis, 51.7% of cases presented with symptoms such as renal colic, urinary tract infection, gross hematuria or severe kidney dysfunction, while 44.8% were incidentally detected kidney stones or mild kidney dysfunction during health checkups or evaluations for unrelated conditions. Genetic analysis was performed in 25 cases, with 23 (85%) identified as type II and only two adult cases of type I included. At diagnosis, kidney dysfunction was noted in 9 cases, including one infant and two patients diagnosed at the time of kidney transplantation for ESKD of unknown cause. The median serum creatinine-based eGFR at diagnosis was lower in adults than in children (41 vs. 102 mL/min/1.73m²), although the difference was not statistically significant (p=0.087). Regarding treatment after diagnosis, 25 cases received xanthine oxidoreductase inhibitors, with 3 of these also receiving citrate preparations and 8 cases undergoing dietary modifications. Four cases underwent lithotripsy or other surgical interventions. During follow-up, none of the 18 cases with over one year of observation experienced recurrence of renal colic or progression of nephrolithiasis. After diagnosis, 25 cases received xanthine oxidase inhibitors, with 3 additionally receiving citrate preparations and 8 undergoing dietary modifications. No recurrence of renal colic or progression of nephrolithiasis was observed in 18 cases followed for over one year. However, among the 4 cases with severe kidney dysfunction at diagnosis, no improvement in kidney function was achieved despite treatment.

To the best of our knowledge, this is the first report clarifying the clinical features of type II APRT deficiency in Japan. Our findings suggest that type II is not necessarily milder, as previous reports on type I showed that untreated or inadequately treated patients remain at risk of progressive and potentially irreversible kidney dysfunction. Further long-term data are needed to optimize management and prognosis.