HUS with mutations in CFH and STEC infection treated with eculizumab in a 4-year-old girl,Pediatric Nephrology

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HUS with mutations in CFH and STEC infection treated with eculizumab in a 4-year-old girl
Pediatric Nephrology ( IF 3 ) Pub Date : 2022-08-15 , DOI: 10.1007/s00467-022-05694-z
Carla Galvez ₁ , Paola Krall _{1,

2} , Alejandro Rojas ₂ , Jun Oh ₃ , Francisco Cano ₁

Affiliation

Background

Hemolytic uremic syndrome secondary to Shiga-toxin-producing Escherichia coli infection (STEC-HUS) generally shows a favorable outcome. Few cases develop extra-renal complications, since neurological involvement is an important cause of morbidity and mortality. The role of complement in STEC-HUS has been recently highlighted, and the use of eculizumab in severe cases has been communicated. HUS results from environmental and genetic factors, but the simultaneous occurrence of STEC and complement mutations remains undetermined.

Methods

A pediatric case with severe STEC-HUS carrying CFH mutations, with favorable response to eculizumab is analyzed.

Results

STEC-HUS was diagnosed in a 4-year-old girl with classic HUS, including low C3. Peritoneal dialysis was started due to hypertension, oligoanuria, and pleural effusion. She evolved with generalized tonic–clonic seizures and required mechanical ventilation. MRI reported multiple supra- and infratentorial ischemic lesions with laminar/striatal cortical necrosis and leukoencephalopathy. After two eculizumab doses, a significative stabilization in diuresis, blood pressure, creatinine, and C3 was achieved. At the third week, episodes of massive digestive bleeding and a life-threatening condition required a colectomy thus preserving the ileocecal valve. Due to atypical evolution, a genetic study was considered, identifying two heterozygous variants (CFH S1191L/V1197A).

Conclusion

STEC-HUS in patients with a genetic predisposition has been previously reported, but the low frequency of occurrence makes it a rare disease. As in the present case, patients with atypical course might benefit from genetic analysis to evaluate early eculizumab initiation and to better understand its phenotype.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

中文翻译：

一名 4 岁女孩接受依库珠单抗治疗并伴有 CFH 突变和 STEC 感染的 HUS

背景

继发于产志贺毒素大肠杆菌感染 (STEC-HUS) 的溶血性尿毒症综合征通常显示出良好的结果。很少有病例出现肾外并发症，因为神经系统受累是发病率和死亡率的重要原因。补体在 STEC-HUS 中的作用最近得到强调，并且在严重病例中使用 eculizumab 已被告知。HUS 是由环境和遗传因素引起的，但 STEC 和补体突变是否同时发生仍未确定。

方法

分析了一例携带CFH突变且对依库珠单抗反应良好的严重 STEC-HUS 儿科病例。

结果

STEC-HUS 被诊断为一名 4 岁女孩，患有经典 HUS，包括低 C3。因高血压、少尿、胸腔积液开始腹膜透析。她发展为全身性强直阵挛发作，需要机械通气。MRI 报告了多处幕上和幕下缺血性病变，伴有层状/纹状体皮质坏死和白质脑病。服用两次 eculizumab 后，利尿、血压、肌酐和 C3 显着稳定。在第三周，大量消化道出血和危及生命的情况需要进行结肠切除术，从而保留回盲瓣。由于非典型进化，考虑了一项遗传研究，确定了两个杂合变体 (CFH S1191L/V1197A)。