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An extremely rare splice site mutation in the gene encoding complement factor I in a patient with atypical hemolytic uremic syndrome
Author(s) -
Ipe Tina S.,
Lim Jooeun,
Reyes Meredith Anne,
Ero Mike,
Leveque Christopher,
Lewis Bradley,
Kain Jamey
Publication year - 2017
Publication title -
journal of clinical apheresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.697
H-Index - 46
eISSN - 1098-1101
pISSN - 0733-2459
DOI - 10.1002/jca.21549
Subject(s) - atypical hemolytic uremic syndrome , eculizumab , medicine , microangiopathic hemolytic anemia , thrombotic microangiopathy , thrombotic thrombocytopenic purpura , factor h , acute kidney injury , hemolytic anemia , gene mutation , gastroenterology , rare disease , mutation , immunology , disease , complement system , antibody , gene , genetics , platelet , biology
Background 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. Study design and methods 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. 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. Conclusion 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.