Ceballos-Picot Irène, Daudon Michel, Harambat Jérôme, Bensman Albert, Knebelmann Bertrand, Bollée Guillaume
a Université Paris Descartes, Assistance Publique Hôpitaux de Paris, Laboratoire de Biochimie Métabolomique et protéomique, Hôpital Necker-Enfants Malades , Paris , France.
Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):241-52. doi: 10.1080/15257770.2013.853780.
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).
腺嘌呤磷酸核糖转移酶（APRT）缺乏症是一种罕见的遗传性代谢紊乱疾病，可导致2,8 - 二羟基腺嘌呤（DHA）在尿液中形成并过度排泄。DHA的低溶解度会导致尿液中晶体沉淀并形成肾结石。该疾病可表现为复发性尿路结石或因晶体沉淀进入肾实质继发的肾病（DHA肾病）。当怀疑存在APRT缺乏症时，现有的诊断工具，包括结石分析、结晶尿检测以及红细胞中的APRT活性检测，使得诊断易于确认。然而，由于对这种代谢紊乱缺乏认识，常常导致诊断和治疗延迟，产生严重后果。早期识别和治疗APRT缺乏症对于预防不可逆转的肾功能丧失至关重要。本综述总结了DHA结石形成和慢性肾病的遗传和代谢机制，以及APRT缺乏症的诊断和管理问题。此外，我们报告了在巴黎内克尔医院生物化学实验室（1978 - 2013年）确诊的64例患者中，51例法国患者（43个家庭），包括22例儿科病例（18个家庭）中导致APRT缺乏症的APRT基因突变情况。
