Department of Nephrology, Centre de Référence des Maladies Rénales Héréditaires, Necker-Enfants Malades Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France.
J Am Soc Nephrol. 2010 Apr;21(4):679-88. doi: 10.1681/ASN.2009080808. Epub 2010 Feb 11.
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder causing 2,8-dihydroxyadenine stones and renal failure secondary to intratubular crystalline precipitation. Little is known regarding the clinical presentation of APRT deficiency, especially in the white population. We retrospectively reviewed all 53 cases of APRT deficiency (from 43 families) identified at a single institution between 1978 and 2009. The median age at diagnosis was 36.3 years (range 0.5 to 78.0 years). In many patients, a several-year delay separated the onset of symptoms and diagnosis. Of the 40 patients from 33 families with full clinical data available, 14 (35%) had decreased renal function at diagnosis. Diagnosis occurred in six (15%) patients after reaching ESRD, with five diagnoses made at the time of disease recurrence in a renal allograft. Eight (20%) patients reached ESRD during a median follow-up of 74 months. Thirty-one families underwent APRT sequencing, which identified 54 (87%) mutant alleles on the 62 chromosomes analyzed. We identified 18 distinct mutations. A single T insertion in a splice donor site in intron 4 (IVS4 + 2insT), which produces a truncated protein, accounted for 40.3% of the mutations. We detected the IVS4 + 2insT mutation in two (0.98%) of 204 chromosomes of healthy newborns. This report, which is the largest published series of APRT deficiency to date, highlights the underdiagnosis and potential severity of this disease. Early diagnosis is crucial for initiation of effective treatment with allopurinol and for prevention of renal complications.
腺嘌呤磷酸核糖基转移酶 (APRT) 缺乏症是一种罕见的常染色体隐性遗传疾病，可导致 2,8-二羟腺嘌呤结石和肾小管内结晶沉淀引起的肾衰竭。关于 APRT 缺乏症的临床表现知之甚少，尤其是在白人中。我们回顾性分析了 1978 年至 2009 年间在一家机构确诊的 53 例 APRT 缺乏症（来自 43 个家系）。诊断时的中位年龄为 36.3 岁（范围 0.5 至 78.0 岁）。在许多患者中，症状出现和诊断之间存在数年的延迟。在有完整临床资料的 40 例来自 33 个家系的患者中，14 例（35%）在诊断时已有肾功能下降。6 例（15%）患者在达到终末期肾病（ESRD）后才得到诊断，其中 5 例在肾移植中疾病复发时做出诊断。8 例（20%）患者在中位随访 74 个月时达到 ESRD。31 个家系进行了 APRT 测序，在分析的 62 条染色体中发现了 54 个（87%）突变等位基因。我们鉴定了 18 种不同的突变。4 号内含子（IVS4）剪接供体位点的单个 T 插入（IVS4 + 2insT）导致截短蛋白，占突变的 40.3%。我们在 204 条健康新生儿染色体中检测到 IVS4 + 2insT 突变，占 0.98%。本报告是迄今为止发表的最大型 APRT 缺乏症系列研究，突出了该疾病的漏诊和潜在严重性。早期诊断对于开始使用别嘌呤醇进行有效治疗以及预防肾脏并发症至关重要。
