Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome.
Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome.
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常染色体隐性遗传性肾近端小管病和高钙尿症：一种新综合征。
DOI：
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发表时间：
2004
影响因子：
13.2
通讯作者：
I. Zelikovic
中科院分区：
文献类型：
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作者：
D. Magen;Lior Adler;H. Mandel;E. Efrati;I. Zelikovic
背景
描述最清楚的原发性遗传性近端肾小管病包括由氯离子通道基因 CLCN5 突变引起的 X 连锁高钙尿性肾结石 (XLHN) 和经典范科尼综合征，其遗传基础尚不清楚。本研究的目的是检查高度近亲血缘关系的德鲁兹家族的临床、生化和遗传特征，该家族患有常染色体隐性遗传性近端肾小管病和高钙尿症（ARPTH），这是一种以前未报道过的综合征。
方法
该家庭的 3 名儿童（2 名女孩，1 名男孩）转诊接受肾糖尿和高钙尿症评估，并对其 10 名近亲进行了临床和生化评估。所有研究参与者都接受了遗传分析，以排除 CLCN5 基因的参与。
结果
对 3 名受影响儿童的评估显示，3 名儿童均出现糖尿、全身性氨基酸尿、低尿酸血症、尿酸尿、低分子量 (LMW) 蛋白尿和高钙尿，2 名儿童出现磷酸尿。他们没有代谢性酸中毒或肾功能不全。一名受影响的女孩患有肾钙质沉着症。两名儿童有生长迟缓病史和代谢性骨病的放射学检查结果。受影响儿童的甲状旁腺激素和 1,25-二羟基维生素 D [1,25(OH)2Vit D] 血液水平正常。检查的未受影响的家庭成员没有肾小管缺陷或 LMW 蛋白尿。遗传连锁分析排除了 ARPTH 表型与 CLCN5 基因座的共分离。
结论
ARPTH 是一种新综合征，其特征为非酸中毒性近端肾小管病、高钙尿症、代谢性骨病和生长迟缓。它与 XLHN 的区别在于其常染色体隐性遗传模式和促钙激素血清水平正常，以及专性携带者不存在 LMW 蛋白尿。 ARPTH 中的突变基因仍有待鉴定。
BACKGROUND
The best described primary inherited proximal tubulopathies include X-linked hypercalciuric nephrolithiasis (XLHN), caused by a mutation in the chloride channel gene CLCN5, and classic Fanconi's syndrome, the genetic basis of which is unknown. The aim of this study is to examine the clinical, biochemical, and genetic characteristics of a highly consanguineous Druze family with autosomal recessive proximal tubulopathy and hypercalciuria (ARPTH), a syndrome not reported previously.
METHODS
Three children (2 girls, 1 boy) of the family referred for evaluation of renal glycosuria and hypercalciuria and 10 of their close relatives were evaluated clinically and biochemically. All study participants underwent genetic analysis to exclude involvement of the CLCN5 gene.
RESULTS
Evaluation of the 3 affected children showed glycosuria, generalized aminoaciduria, hypouricemia, uricosuria, low molecular weight (LMW) proteinuria, and hypercalciuria in all 3 children and phosphaturia in 2 children. They had no metabolic acidosis or renal insufficiency. One affected girl had nephrocalcinosis. Two children had a history of growth retardation and radiological findings of metabolic bone disease. Parathyroid hormone and 1,25-dihydroxyvitamin D [1,25(OH)2Vit D] blood levels in affected children were normal. Unaffected family members examined had no renal tubular defects or LMW proteinuria. Genetic linkage analysis excluded cosegregation of the ARPTH phenotype with the CLCN5 locus.
CONCLUSION
ARPTH is a new syndrome characterized by nonacidotic proximal tubulopathy, hypercalciuria, metabolic bone disease, and growth retardation. It can be distinguished from XLHN by its autosomal recessive mode of inheritance and normal serum levels of calciotropic hormones, as well as the absence of LMW proteinuria in obligate carriers. The gene mutated in ARPTH remains to be identified.