2,8-Dihydroxyadenine Urolithiasis: A Not So Rare Inborn Error of Purine Metabolism |
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Authors: | Irène Ceballos-Picot Michel Daudon Jérôme Harambat Albert Bensman Bertrand Knebelmann Guillaume Bollée |
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Institution: | 1. Université Paris Descartes, Assistance Publique H?pitaux de Paris, Laboratoire de Biochimie Métabolomique et protéomique, H?pital Necker-Enfants Malades, Paris, Franceirene.ceballos@nck.aphp.fr;3. Service D’explorations Fonctionnelles H?pital Tenon, Paris, France;4. Centre Hospitalier Universitaire de Bordeaux, Service de Pédiatrie, Centre de Référence Maladies Rénales Rares du Sud Ouest, Bordeaux, France;5. Université Pierre-Marie Curie, APHP, Service de Néphrologie Pédiatrique, H?pital Armand Trousseau, Paris, France;6. Université Paris Descartes, Assistance Publique H?pitaux de Paris, Service de Néphrologie, H?pital Necker-Enfants Malades, Paris, France;7. Association pour l’Utilisation du Rein Artificiel and Inserm U970, Paris, France |
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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). |
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Keywords: | Enzymology gene regulation mechanism of action studies nucleoside synthesis polymerase chain reaction/PCR |
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