Subject(s)
Asian People/genetics , Atypical Hemolytic Uremic Syndrome/genetics , Diacylglycerol Kinase/genetics , Mutation, Missense , Antibodies, Monoclonal, Humanized/therapeutic use , Atypical Hemolytic Uremic Syndrome/diagnosis , Atypical Hemolytic Uremic Syndrome/drug therapy , Atypical Hemolytic Uremic Syndrome/enzymology , Atypical Hemolytic Uremic Syndrome/ethnology , Child, Preschool , DNA Mutational Analysis , Databases, Factual , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Hypertension/enzymology , Hypertension/ethnology , Hypertension/genetics , Infant , Infant, Newborn , Japan , Male , Phenotype , Treatment OutcomeABSTRACT
BACKGROUND: Severe hypertension (HTN) and acute kidney injury frequently associated with atypical hemolytic uremic syndrome (aHUS) were refractory to various therapies in the pre-eculizumab era. Here we report the case of a 4-month-old boy who developed aHUS presenting with undetectable C3 protein, no predisposing mutations in complement factors, and no antibodies against factor H. METHODS: Repeated plasma infusions and nine sessions of plasmapheresis were ineffective. The patient initially required continuous hemodiafiltration and thereafter peritoneal dialysis. Despite vigorous antihypertensive treatment and improved fluid overload with dialysis, HTN persisted. His low C3 level (<20 mg/dl) suggested unrestricted complement activation. Therefore, based on the suspicion of unrestricted complement cascade in the pathogenesis, treatment with eculizumab, a human anti-C5 monoclonal antibody, was initiated with the aim of controlling disease activity. RESULTS: Eculizumab therapy resulted in the control of severe HTN and cessation of peritoneal dialysis. CONCLUSIONS: This infant with HTN and acute kidney injury associated with aHUS was treated successfully with eculizumab.
