TY - JOUR
T1 - An extremely rare splice site mutation in the gene encoding complement factor I in a patient with atypical hemolytic uremic syndrome
AU - Ipe, Tina S.
AU - Lim, Jooeun
AU - Reyes, Meredith Anne
AU - Ero, Mike
AU - Leveque, Christopher
AU - Lewis, Bradley
AU - Kain, Jamey
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/12
Y1 - 2017/12
N2 - 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.
AB - 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.
KW - CFI
KW - aHUS
KW - eculizumab
KW - novel mutation
KW - thrombotic microangiopathy
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U2 - 10.1002/jca.21549
DO - 10.1002/jca.21549
M3 - Article
C2 - 28455885
AN - SCOPUS:85018259474
SN - 0733-2459
VL - 32
SP - 584
EP - 588
JO - Journal of Clinical Apheresis
JF - Journal of Clinical Apheresis
IS - 6
ER -