hemolytic uremic syndrome

Etiology

 E. coli-associated SHU

 nondiarrheal, nonverocytotoxin SHU (atypical SHU)

• mutations in the complement regulator factor-H in 15-30% of patients with atypical hemolytic uremic syndrome (HUS)(12424708)

 mutations of the CD46 gene in atypical hemolytic uremic syndrome (HUS)

• heterozygous deletion resulting in the intracellular retention of the mutant protein
• different heterozygous deletion leading to a premature stop codon and the loss of the C-terminus
• substitution (S206P) resulting in cell-surface expression but inefficient inactivation of surface-bound C3b
• membrane cofactor protein (MCP, CD46) is a widely expressed transmembrane complement regulator. As does the soluble regulator factor-H, it inhibits complement activation by inactivating the C3b that is deposited on target membranes.

 bone marrow allograft

See also

 thrombotic thrombocytopenic purpura
 atypical hemolytic uremic syndrome

References

 Siegler R, Oakes R. Hemolytic uremic syndrome; pathogenesis, treatment, and outcome. Curr Opin Pediatr. 2005 Apr;17(2):200-4. PMID: 15800412

 Goodship TH, Liszewski MK, Kemp EJ, Richards A, Atkinson JP. Mutations in CD46, a complement regulatory protein, predispose to atypical HUS. Trends Mol Med. 2004 May 1;10(5):226-231. PMID: 15121049

 Richardson SE, Karmali MA, Becker LE, Smith CR. The histopathology of the hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli infections. Hum Pathol. 1988 Sep;19(9):1102-8. PMID: 3047052