Novel Complement Factor H mutation, a case report of atypical hemolytic uremic syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare but catastrophic disease. It is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. When the aHUS is primary, the cause is due to mutations in proteins that regulate the alternative pathway of complement, such as Factor H, Factor I, Factor B, C3, Membrane Co-Factor Protein and Thrombomodulin. Usually primary aHUS is associated with other amplifiers complement factors. We present a case of aHUS in a 25-year-old female patient; she presented with malignant hypertension and severe renal failure. After a widespread study, the etiology of the aHUS was a mutation in the complement factor H, not previously described in the literature (p.Tyr1177His). After treatment with Eculizumab (C5 inhibitor monoclonal antibody), she recovered renal function with not hemodialysis requirements.

Síndrome hemolítico urémico atípico

“…La duración del tratamiento es controversial, al menos, el tratamiento debiera mantenerse durante el período de mayor riesgo, el cual se produce dentro del primer año de un primer episodio. Se recomienda tratamiento indefinido en mutaciones de mal pronóstico (CFH, CFHR, C3 y CFB), trasplante renal, recaídas frecuentes y cuando hubo riesgo vital por SHUa 12,17,24 .…”

Deleterious Impact of a Novel CFH Splice Site Variant in Atypical Hemolytic Uremic Syndrome

“…Complement factor H is a 155 kDa plasma protein that consists of 20 homologous short consensus repeat (SCR) domains of 60 amino acids length, each containing 4 conserved cystein residues that form two structure-defining disulfide-bridges. The region spanning SCR1-4 has been proposed to act as regulatory domain, mediating C3b binding in fluid phase, CFI interaction and convertase decay accelerating activity (Goicoechea de Jorge et al, 2013; Perkins et al, 2014; Clark and Bishop, 2015; de Vriese et al, 2015; Sepúlveda et al, 2016). Whereas SCR6, SCR7, and SCR12-14 seem to be additionally involved in glycosaminoglycan (GAG) or C3b binding, SCR19 and SCR20 predominantly serve as surface-binding domain, comprising the ability to interact with both GAGs and C3b at self-membranes.…”