Review
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World J Clin Urol. Nov 24, 2014; 3(3): 218-226
Published online Nov 24, 2014. doi: 10.5410/wjcu.v3.i3.218
Adenine phosphoribosyltransferase deficiency: Leave no stone unturned
Guillaume Bollée, Michel Daudon, Irène Ceballos-Picot
Guillaume Bollée, Division of Nephrology and Research Center of the Centre Hospitalier de l’Université de Montréal and Université de Montréal, Montréal, Québec H2L 4M1, Canada
Michel Daudon, Service d’Explorations Fonctionnelles, Assistance Publique Hôpitaux de Paris, Hôpital Tenon, 75020 Paris, France
Irène Ceballos-Picot, Université Paris Descartes, Assistance Publique Hôpitaux de Paris, Laboratoire de Biochimie Métabolomique et protéomique, Hôpital Necker-Enfants Malades, 75015 Paris, France
Author contributions: Bollée G contributed to the literature search, study design and wrote the review; Daudon M and Ceballos-Picot I contributed to the literature search, study design and discussion about the content of the article.
Correspondence to: Dr. Guillaume Bollée, Division of Nephrology and Research Center of the Centre Hospitalier de l’Université de Montréal and Université de Montréal, Montréal, Québec H2L 4M1, Canada. guillaume.bollee.chum@ssss.gouv.qc.ca
Telephone: +1-514-8908000 Fax: +1-514-4127831
Received: May 2, 2014
Revised: June 4, 2014
Accepted: July 25, 2014
Published online: November 24, 2014
Processing time: 201 Days and 13.8 Hours
Abstract

Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disease leading to generation of large amounts of 2,8-dihydroxyadenine (DHA). DHA is excreted in urine, where it precipitates into crystals due to its low solubility. DHA crystals can aggregate into stones or cause injury to the renal parenchyma (DHA nephropathy). Recurrent urolithiasis and DHA nephropathy are the two clinical manifestations of APRT deficiency. Diagnosis of APRT deficiency can be made during childhood as well as adulthood. Diagnosis mainly relies on the recognition of DHA in stones or urine crystals. Measurement of APRT activity and genetic testing are useful for confirmation of diagnosis, for family screening and should be considered in difficult cases of urolithiasis or crystalline nephropathy. Allopurinol therapy is the cornerstone of treatment and is highly effective in preventing recurrence of stones and kidney disease. High fluid intake and dietary modifications are also recommended. Early diagnosis and treatment are of paramount importance to prevent renal damage. Unfortunately, diagnosis of APRT deficiency is often overlooked and irreversible renal failure still occurs in a substantial proportion of patients. Clinicians must be alert to the possibility of APRT deficiency and consider the appropriate diagnostic tests in certain cases. This review discusses the genetic and biochemical mechanisms of APRT deficiency, and the issues of diagnosis and management.

Keywords: Adenine phosphoribosyltransferase; Dihydroxyadenine; Urolithiasis; Crystalline nephropathy; 2,8-dihydroxyadenine nephropathy

Core tip: Adenine phosphoribosyltransferase (APRT) deficiency is a rare but underrecognized genetic disease causing recurrent dihydroxyadenine urolithiasis and crystalline nephropathy. Clinical presentation is variable and diagnosis can be made at any age. Treatment with a xanthine dehydrogenase inhibitor is highly effective in preventing recurrence of stones and kidney disease. Unfortunately, diagnosis of APRT deficiency is often overlooked and irreversible renal failure still occurs in a substantial proportion of affected individuals. Early diagnosis is of paramount importance to prevent long term complications.