Phenotype and Genotype Characterization of Adenine Phosphoribosyltransferase Deficiency
Phenotype and Genotype Characterization of Adenine Phosphoribosyltransferase Deficiency
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DOI：
10.1681/asn.2009080808
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发表时间：
2010-04-01
影响因子：
13.6
通讯作者：
Ceballos-Picot, Irene
中科院分区：
文献类型：
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作者：
Bollee, Guillaume;Dollinger, Cecile;Ceballos-Picot, Irene
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病，可引起2，8-二羟基腺嘌呤结石和继发于肾小管内结晶沉淀的肾衰竭。关于APRT缺乏症的临床表现知之甚少，特别是在白色人群中。我们回顾性分析了1978年至2009年期间在一家机构发现的所有53例APRT缺乏症（来自43个家庭）。诊断时的中位年龄为36.3岁（范围为0.5至78.0岁）。在许多患者中，症状的出现和诊断之间有几年的延迟。在来自33个家庭的40例患者中，有完整的临床数据，14例（35%）在诊断时肾功能下降。6例（15%）患者在达到终末期肾病后确诊，其中5例在肾移植术后疾病复发时确诊。8例（20%）患者在中位随访74个月期间达到ESRD。31个家庭进行了APRT测序，确定了54（87%）突变等位基因的62条染色体上分析。我们发现了18种不同的突变。在内含子4的剪接供体位点（IVS 4 + 2 insT）的单个T插入，产生截短的蛋白质，占突变的40.3%。我们在204条健康新生儿染色体中检测到2条（0.98%）IVS 4 + 2 insT突变。这份报告是迄今为止最大的APRT缺陷系列出版物，强调了这种疾病的诊断不足和潜在严重性。早期诊断对于开始有效的别嘌呤醇治疗和预防肾脏并发症至关重要。
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.