Atypical hemolytic uremic syndrome in children

Abstract

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. We studied a Korean pediatric cohort to delineate the various etiologies and clinical characteristics. Methods: A multicenter cohort of 51 Korean children with aHUS was screened for mutations by targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibodies (anti-CFH) titers were measured. Multiplex ligation dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein (CFHR) genes. We grouped the patients according to the etiology and compared the clinical features using the Mann-Whitney U test and chi-square test. Results: Fifteen patients (Group A, 29.7%) had anti-CFH and mutations were detected in 11 (Group B, 21.6%) patients, including one with combined mutations. The remaining 25 (Group C, 49.0%) were neither–positive. Anti-CFH-association was more frequent than the world-wide prevalence. Group A showed older onset age than Group B. Group B showed worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in Group A, Group B+C and the control, respectively. Conclusions: In our cohort, we observed a relatively high incidence of anti-CFH-association. Clinical outcomes largely conformed to the previous reports. Although the size is limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.