Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity.
Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity.
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DOI：
10.1007/s00467-016-3399-0
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发表时间：
2017-05
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影响因子：
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通讯作者：
Kömhoff M
中科院分区：
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作者：
Beck BB;van Spronsen F;Diepstra A;Berger RM;Kömhoff M
甲基丙二酸尿症和同型胱氨酸尿症，钴胺素C（cblC）型，是功能性钴胺素（维生素B12）缺乏症最常见的遗传类型。这种代谢性疾病的特征是神经认知疾病（小头畸形、癫痫发作、发育迟缓、共济失调、张力减退）的显著异质性和可变的中枢外神经系统受累（发育不良、心血管、肾脏、眼部），主要表现在生命早期，有时在妊娠期间。为了提高对cblC缺陷相关肾脏疾病的认识和理解，我们研究了36例患者的生化、遗传、临床和组织病理学数据。所有患者一致的肾脏疾病临床化学特征为血管内溶血、血尿和蛋白尿，3例患者观察到肾病范围的蛋白尿。肾功能范围从正常到肾衰竭，8例患者需要（间歇性）透析。三分之二的人被诊断为非典型（梅毒阴性）溶血性尿毒综合征（HUS）。16例患者活检标本的肾组织病理学分析显示，肾小球病变典型的血栓性微血管病（TMA）。羟钴胺素治疗改善了大多数患者的肾功能，包括3例可以停止透析的患者。在44%的患者中观察到神经系统后遗症，在39%的患者中观察到心肺受累，后一组中有一半表现出肺动脉高压。未经治疗的患者死亡率达到100%，心肺或神经系统受累患者死亡率分别为79%和56%。在所有表现为不明确的血管内溶血、血尿和蛋白尿的患者中，应通过测定血液/血浆同型半胱氨酸水平和/或基因检测排除cblC缺陷，无论实际肾功能和神经系统状态如何，以确保及时诊断和治疗。本文的在线版本（doi：10.1007/s 00467 -016-3399-0）包含补充材料，可供授权用户使用。
Methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type, is the most common genetic type of functional cobalamin (vitamin B12) deficiency. This metabolic disease is characterized by marked heterogeneity of neurocognitive disease (microcephaly, seizures, developmental delay, ataxia, hypotonia) and variable extracentral nervous system involvement (failure to thrive, cardiovascular, renal, ocular) manifesting predominantly early in life, sometimes during gestation. To enhance awareness and understanding of renal disease associated with cblC defect, we studied biochemical, genetic, clinical, and histopathological data from 36 patients. Consistent clinical chemistry features of renal disease were intravascular hemolysis, hematuria, and proteinuria in all patients, with nephrotic-range proteinuria observed in three. Renal function ranged from normal to renal failure, with eight patients requiring (intermittent) dialysis. Two thirds were diagnosed with atypical (diarrhea-negative) hemolytic uremic syndrome (HUS). Renal histopathology analyses of biopsy samples from 16 patients revealed glomerular lesions typical of thrombotic microangiopathy (TMA). Treatment with hydroxycobalamin improved renal function in the majority, including three in whom dialysis could be withdrawn. Neurological sequelae were observed in 44 % and cardiopulmonary involvement in 39 % of patients, with half of the latter group demonstrating pulmonary hypertension. Mortality reached 100 % in untreated patients and 79 and 56 % in those with cardiopulmonary or neurological involvement, respectively. In all patients presenting with unclear intravascular hemolysis, hematuria, and proteinuria, cblC defect should be ruled out by determination of blood/plasma homocysteine levels and/or genetic testing, irrespective of actual renal function and neurological status, to ensure timely diagnosis and treatment. The online version of this article (doi:10.1007/s00467-016-3399-0) contains supplementary material, which is available to authorized users.