携 DGKE 基因纯合突变的非典型溶血尿毒综合征伴低补体 C3 患者对依库珠单抗治疗反应良好：一例报告。
A patient with a homozygous diacylglycerol kinase epsilon (DGKE) gene mutation with atypical haemolytic uraemic syndrome and low C3 responded well to eculizumab: a case report.
机构信息
Department of Paediatrics, College of Medicine, King Faisal University, Alhasa, Saudi Arabia.
Department Paediatric Nephrology, King Abdullah Specialists Children Hospital, Riyadh, Saudi Arabia.
出版信息
BMC Nephrol. 2021 Apr 20;22(1):140. doi: 10.1186/s12882-021-02352-8.
BACKGROUND
Atypical haemolytic uraemic syndrome (aHUS) is a rare systemic syndrome characterized by non-immune haemolytic anaemia, thrombocytopenia, and kidney injury. In most cases, alternative complement pathway dysregulation is the identifying cause. Recently, other genetic causes have been identified, including a mutation in the diacylglycerol kinase epsilon (DGKE) gene, which theoretically affect the coagulation pathway and does not affect the complement pathway. Data about the management of these patients are limited. Ideal management and definitive treatment protocols have not yet been established.
CASE PRESENTATION
A three-year-old boy presented with features of atypical haemolytic uraemic syndrome (aHUS) and low complement C3. He was presumed to have complement-mediated aHUS and was managed empirically with eculizumab. Two weeks after starting eculizumab, his haemoglobin levels, platelet count, and complement C3 level normalized but he continued to have non-nephrotic range proteinuria. His genetic testing revealed a homozygous DGKE mutation, with no other mutation detected. Six months after presentation, the patient was still in remission with no features of aHUS, a trial of weaning eculizumab by increasing dose interval was followed by nephrotic range proteinuria and severe oedema. His proteinuria improved and his oedema resolved after resuming his recommended eculizumab dose.
CONCLUSIONS
DGKE gene mutation can lead to aHUS with theoretically no complement dysregulation. However, some patients with this mutation show alternative complement pathway activation. This case report describes a patient with aHUS due to a DGKE gene mutation and low C3 levels who responded to eculizumab, adding to the previously reported cases of patients with DGKE gene mutations who had complete remission with no relapse with C5 blockers and/or plasma exchange. A randomized controlled study on patients with DGKE mutations might be beneficial in understanding the disease and generating a management protocol.
背景
非典型溶血性尿毒症综合征（aHUS）是一种罕见的全身性综合征，其特征为非免疫性溶血性贫血、血小板减少和肾脏损伤。在大多数情况下，替代补体途径失调是确定的病因。最近，已经确定了其他遗传病因，包括二酰基甘油激酶 ε（DGKE）基因突变，该基因突变理论上会影响凝血途径而不影响补体途径。关于这些患者的管理数据有限。理想的管理和明确的治疗方案尚未建立。
病例介绍
一名三岁男孩出现非典型溶血性尿毒症综合征（aHUS）和补体 C3 降低的特征。他被认为患有补体介导的 aHUS，并接受依库珠单抗的经验性治疗。依库珠单抗治疗开始后两周，他的血红蛋白水平、血小板计数和补体 C3 水平恢复正常，但仍有非肾病范围的蛋白尿。他的基因检测显示 DGKE 基因突变纯合子，未检测到其他突变。发病 6 个月后，患者仍处于缓解期，无 aHUS 特征，尝试通过增加剂量间隔逐渐停用依库珠单抗，随后出现肾病范围蛋白尿和严重水肿。重新使用推荐剂量的依库珠单抗后，他的蛋白尿改善，水肿消退。
结论
DGKE 基因突变可导致 aHUS，理论上不存在补体失调。然而，一些患有该突变的患者表现出替代补体途径的激活。本病例报告描述了一名因 DGKE 基因突变和 C3 水平降低导致的 aHUS 患者，他对依库珠单抗有反应，这增加了先前报道的 DGKE 基因突变患者的病例，这些患者使用 C5 抑制剂和/或血浆置换完全缓解，且无复发。对 DGKE 基因突变患者进行随机对照研究可能有助于了解该疾病并制定管理方案。
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