FAMILIAL HEMOLYTIC-UREMIC SYNDROME AND HOMOZYGOUS FACTOR-H DEFICIENCY

Inherited hemolytic-uremic syndrome (HUS) is unusual. We report the oc currence of HUS in two siblings; one died at an early age while the ot her (the proband) has presented with three episodes of HUS since the a ge of 19 years. The finding of a persistently low serum C3 level in th is patient led to a thorough evaluation of her complement cascade and a family investigation. The proband and her asymptomatic younger siste r were found to have very low serum levels (5% of normal) of factor H, a regulatory protein of the alternative complement pathway. Both pati ents had low levels of serum C3, factor B, CH50 and VAH50, reflecting persistent alternative pathway activation. The father and mother both had half-normal serum factor H levels but an otherwise normal compleme nt profile. Other members of the extended pedigree were also found to have half-normal serum factor H levels. In conclusion, in this family, factor H deficiency appears to be associated with HUS and is transmit ted as an autosomal recessive trait. Persistent C3 hypocomplementemia in the setting of familiar and/or recurrent HUS should be a clue to a possible inherited complement deficiency. (C) 1994 by the National Kid ney Foundation, Inc.