Atypical haemolytic-uraemic syndrome due to heterozygous mutations of CFH/CFHR1-3 and complement factor H 479.

Abstract

Atypical haemolytic-uraemic syndrome (aHUS) is characterised by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure in the absence of shigatoxin1. aHUS is rare, accounting for approximately 10% of all cases of HUS, and has a poor prognosis2. aHUS can occur at any age and may be sporadic or familial. It is now known that aHUS is due to the loss of complement regulation resulting from mutations in the complement regulatory proteins complement factor H (CFH), factor I, complement factor H related (CFHR)1–3, CFHR-5, CD46 membrane cofactor protein (MCP), thrombomodulin (THBD) or complement activators such as factor B, and complement 3 (C3)2,3. The presence of a mutation, or variant (single nucleotide polymorphisms and haplotype blocks), and a triggering event increasing complement activation may be necessary for manifestation of the disease4,5. In this paper we report the onset of aHUS in association with heterozygous deletion of CFHR1 and a mutation in CFH, c.497G>T (p.Arg166Leu) that has not previously been reported with aHUS. We also report this patient’s response to complement inhibition with eculizumab and the effect of the patient’s subsequent pregnancy.