Recurrent atypical hemolytic uremic syndrome associated with factor I mutation in a living related renal transplant recipient

Abstract

Atypical hemolytic uremic syndrome, or the nondiarrheal form of hemolytic uremic syndrome, is a rare disorder typically classified as familial or sporadic. Recent literature has suggested that approximately 50% of patients have mutations in factor H (CFH), factor I (CFI), or membrane cofactor protein (encoded by CD46). Importantly, results of renal transplantation in patients with mutations in either CFH or CFI are dismal, with recurrent disease leading to graft loss in the majority of cases. We describe an adult renal transplant recipient who developed recurrent hemolytic uremic syndrome 1 month after transplantation. Bidirectional sequencing of CFH, CFI, and CD46 confirmed that the patient was heterozygous for a novel missense mutation, a substitution of a serine reside for a tyrosine residue at amino acid 369, in CFI. This report reemphasizes the importance of screening patients with atypical hemolytic uremic syndrome for mutations in these genes before renal transplantation and shows the challenges in the management of these patients.

Figure 1

(A) –PAS-stained allograft biopsy (400×) reveals intracapillary fibrin thrombi (arrowhead), moderate increase in mesangial matrix and cellularity and global reduplication of glomerular capillary walls. A small capillary (top left corner) also shows a luminal fibrin thrombus. (B) PAMM Silver stained section (400×) shows another glomerulus with moderate increase in mesangial matrix and cellularity, and highlights the splitting of glomerular capillary walls. Luminal fibrin thrombi (arrowhead) are also noted.

Figure 2

A heterozygous missense mutation c.1106A>C, p.Tyr369Ser lies in the serine protease domain of Factor I.

Figure 3

Mutations in complement factor I associated with aHUS. Novel mutation Y369S noted with asterisk * Used with full permission from Oxford University Press