Abstract：
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy.
METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed.
RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant.
CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.
METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed.
RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant.
CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.
摘要：
背景：非典型溶血性尿毒综合征（aHUS）是一种危及生命的血栓性微血管病。已经在60-70%的个体中鉴定了替代补体(AP)途径中的遗传缺陷。Eculizumab被推荐为一线治疗。
方法：我们收集了1例伴有蛋白丢失性肠病（PLE）的aHUS患儿的临床资料。进行基因检测。综述了aHUS联合PLE的相关文献。
结果：一名15岁的中国女孩在3.7岁时被诊断出患有aHUS，经历了5次发作；她的症状通过血浆治疗完全缓解。首次发作后出现严重的胃肠道症状和低蛋白血症，PLE被诊断出来。鉴定了一种新的纯合CD46变体，和FACS显示CD46表达显着降低。她在最近复发时表现出持续的胃肠道症状和头痛，并进展为慢性肾衰竭；开始腹膜透析。最后一次复发后8个月给予Eculizumab。令人惊讶的是,PLE治愈了。之后,透析中断,eGFR恢复到44.8ml/min/1.73m2。对文献的回顾表明，血栓形成的PLE是由CD55变体通过AP系统的过度激活引起的。我们报告了1例CD46变异引起PLE的aHUS患者。在我们的患者和使用依库珠单抗治疗的CD55变体患者中，PLE和aHUS的症状均显着缓解，表明PLE是我们患有CD46变异的患者的aHUS的新症状。
结论：我们的病例扩展了由CD46突变引起的aHUS表型，并提供了长期慢性肾衰竭后依库珠单抗疗效的证据。
方法：我们收集了1例伴有蛋白丢失性肠病（PLE）的aHUS患儿的临床资料。进行基因检测。综述了aHUS联合PLE的相关文献。
结果：一名15岁的中国女孩在3.7岁时被诊断出患有aHUS，经历了5次发作；她的症状通过血浆治疗完全缓解。首次发作后出现严重的胃肠道症状和低蛋白血症，PLE被诊断出来。鉴定了一种新的纯合CD46变体，和FACS显示CD46表达显着降低。她在最近复发时表现出持续的胃肠道症状和头痛，并进展为慢性肾衰竭；开始腹膜透析。最后一次复发后8个月给予Eculizumab。令人惊讶的是,PLE治愈了。之后,透析中断,eGFR恢复到44.8ml/min/1.73m2。对文献的回顾表明，血栓形成的PLE是由CD55变体通过AP系统的过度激活引起的。我们报告了1例CD46变异引起PLE的aHUS患者。在我们的患者和使用依库珠单抗治疗的CD55变体患者中，PLE和aHUS的症状均显着缓解，表明PLE是我们患有CD46变异的患者的aHUS的新症状。
结论：我们的病例扩展了由CD46突变引起的aHUS表型，并提供了长期慢性肾衰竭后依库珠单抗疗效的证据。
