Alternative titles; symbols
ORPHA: 2134, 544472;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 19p13.3 | {Hemolytic uremic syndrome, atypical, susceptibility to, 5} | 612925 | Autosomal dominant | 3 | C3 | 120700 |
A number sign (#) is used with this entry because susceptibility to the development of atypical hemolytic uremic syndrome-5 (AHUS5) can be conferred by mutation in the gene encoding complement component-3 (C3; 120700).
Atypical hemolytic uremic syndrome-5 (AHUS5) is characterized by nonimmune hemolytic anemia, thrombocytopenia, and renal impairment, in the absence of infection with Stx-producing bacteria or streptococci (summary by Noris and Remuzzi, 2009).
For a general phenotypic description and a discussion of genetic heterogeneity of aHUS, see AHUS1 (235400).
Reviews
Noris and Remuzzi (2009) provided a detailed review of atypical HUS.
Fremeaux-Bacchi et al. (2008) reported 11 probands with atypical HUS. Further pedigree analysis showed that 1 proband had 2 additional affected family members and another had 1 additional affected family member. Age at onset ranged from 8 months to 40 years. Most developed end-stage renal disease, and all had decreased serum C3. Six patients had undergone renal transplantation, 3 of whom had recurrence of the disease after transplantation.
In 11 probands with atypical HUS, Fremeaux-Bacchi et al. (2008) identified 9 different heterozygous mutations in the C3 gene (see, e.g., 120700.0005-120700.0008). Five of the mutations resulted in a gain of function with resistance to degradation by MCP (120920) and CFI (217030), and 2 resulted in haploinsufficiency. Family history, when available, showed decreased penetrance.
Noris and Remuzzi (2009) noted that about 4 to 10% of aHUS patients have heterozygous mutations in the C3 gene, and these patients usually have low C3 levels.
Fremeaux-Bacchi, V., Miller, E. C., Liszewski, M. K., Strain, L., Blouin, J., Brown, A. L., Moghal, N., Kaplan, B. S., Weiss, R. A., Lhotta, K., Kapur, G., Mattoo, T., and 14 others. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome. Blood 112: 4948-4952, 2008. [PubMed: 18796626] [Full Text: https://doi.org/10.1182/blood-2008-01-133702]
Noris, M., Remuzzi, G. Atypical hemolytic-uremic syndrome. New Eng. J. Med. 361: 1676-1687, 2009. [PubMed: 19846853] [Full Text: https://doi.org/10.1056/NEJMra0902814]