Pathogenic gain-of-function variants in
complement Factor B were identified as causative of
atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of
complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe
hypertension which required 6
anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed
end-stage renal disease at the age of 3 years.
Hypertension and vascular symptoms persisted while he was on
peritoneal dialysis or
hemodialysis, as well as after bilateral
nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in
Factor B (K323E) was found. A combined liver and
kidney transplantation (CLKT) was performed in March 2009, since there was not any
therapy for
complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after
transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell
non-Hodgkin lymphoma that was cured by
chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with
cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.