Ipe Tina S, Lim Jooeun, Reyes Meredith Anne, Ero Mike, Leveque Christopher, Lewis Bradley, Kain Jamey
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.
Machaon Diagnostics, Oakland, California.
J Clin Apher. 2017 Dec;32(6):584-588. doi: 10.1002/jca.21549. Epub 2017 Apr 28.
Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney failure. The disease is difficult to diagnose due to its similarity with other hematologic disorders, such as thrombotic thrombocytopenic purpura (TTP). However, genetic mutations are found in 50-70% of patients with aHUS and can be useful in its diagnosis.
A 40-year-old male presented to our hospital with acute kidney injury, evidenced by high creatinine levels (8.3 mg/dL) and kidney biopsy results. The patient was preliminarily diagnosed with TTP and therapeutic plasma exchange (TPE) was initiated. After four treatments, TPE was discontinued due to lack of ADAMTS13 activity and inhibitor assay results that were not consistent with TTP, improved hematologic laboratory results, and aHUS genetic testing results.
Next-generation sequencing showed a rare mutation at a splice site in the gene encoding complement factor I (CFI). Implication of this mutation in aHUS has not been previously described. Treatment with eculizumab reduced creatinine levels below 4.0 mg/dL, and the patient remained on maintenance dosage of eculizumab (1200 mg/14 days) to prevent aHUS recurrence.
An extremely rare, heterozygous mutation in the gene encoding CFI likely affecting splicing was associated for the first time with aHUS. Sequencing was critical for rapid diagnosis and subsequent timely treatment with eculizumab, which resulted in improved renal function.
非典型溶血尿毒综合征（aHUS）是一种罕见疾病，其特征为血小板减少、微血管病性溶血性贫血和急性肾衰竭。由于该疾病与其他血液系统疾病（如血栓性血小板减少性紫癜（TTP））相似，故难以诊断。然而，50%至70%的aHUS患者存在基因突变，这对其诊断可能有用。
一名40岁男性因急性肾损伤就诊于我院，高肌酐水平（8.3mg/dL）及肾活检结果证实了这一点。该患者初步诊断为TTP，并开始进行治疗性血浆置换（TPE）。经过四次治疗后，由于缺乏ADAMTS13活性且抑制剂检测结果与TTP不符、血液学实验室结果改善以及aHUS基因检测结果，TPE被停用。
二代测序显示编码补体因子I（CFI）的基因剪接位点存在罕见突变。此前尚未描述该突变在aHUS中的意义。使用依库珠单抗治疗后，肌酐水平降至4.0mg/dL以下，患者继续接受依库珠单抗维持剂量治疗（1200mg/14天）以预防aHUS复发。
编码CFI的基因中一种极罕见的杂合突变可能影响剪接，首次与aHUS相关联。测序对于快速诊断及随后及时使用依库珠单抗治疗至关重要，依库珠单抗治疗使肾功能得到改善。
