title: 2,8-Dihydroxyadenine urolithiasis: a not so rare inborn error of purine metabolism.
abstract: Adenine phosphoribosyltransferase (APRT) deficiency is a rare inherited metabolic disorder that leads to the formation and hyperexcretion of 2,8-dihydroxyadenine (DHA) into urine. The low solubility of DHA results in precipitation and formation of urinary crystals and kidney stones. The disease can be present as recurrent urolithiasis or nephropathy secondary to crystal precipitation into renal parenchyma (DHA nephropathy). The diagnostic tools available, including stone analysis, crystalluria, and APRT activity in red blood cells, make the diagnosis easy to confirm when APRT deficiency is suspected. However, the lack of recognition of this metabolic disorder frequently resulted in a delay in diagnosis and treatment with grave consequences. The early recognition and treatment of APRT deficiency are of crucial importance to prevent irreversible loss of renal function. This review summarizes the genetic and metabolic mechanisms underlying DHA stones formation and chronic kidney disease, along with the issues of diagnosis and management of APRT deficiency. Moreover, we report the mutations in the APRT gene responsible for APRT deficiency in 51 French patients (43 families) including 22 pediatric cases (18 families) among the 64 patients identified in the biochemistry laboratories of Necker Hospital, Paris (1978-2013).
authors.affiliation: a Université Paris Descartes, Assistance Publique Hôpitaux de Paris, Laboratoire de Biochimie Métabolomique et protéomique, Hôpital Necker-Enfants Malades , Paris , France.
authors.forename: Irène
authors.initials: I
authors.lastname: Ceballos-Picot
authors.forename: Michel
authors.initials: M
authors.lastname: Daudon
authors.forename: Jérôme
authors.initials: J
authors.lastname: Harambat
authors.forename: Albert
authors.initials: A
authors.lastname: Bensman
authors.forename: Bertrand
authors.initials: B
authors.lastname: Knebelmann
authors.forename: Guillaume
authors.initials: G
authors.lastname: Bollée
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000172:deficiency* / Q000378:metabolism; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy; D015995:Prevalence; D052878:Urolithiasis / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism / Q000628:therapy
chemical_list: D000228:Adenine Phosphoribosyltransferase
keywords: Enzymology; gene regulation; mechanism of action studies; nucleoside synthesis; polymerase chain reaction/PCR