A deficiency of complement regulatory proteins has been associated with atypical (non-diarrheal) hemolytic uremic syndrome (HUS). Patients with heterozygous mutations in factor H, factor I, and CD46 (membrane cofactor protein) can develop atypical HUS. Up to 50% of patients with atypical
HUS have a defect in one of these three complement proteins.
Factor H and I regulate C3: a homozygous complete deficiency in either factor leads to C3 consumption through alternative pathway activation and predisposes patients to severe pyogenic bacterial infections.