Hemolytic Uremic Syndrome, Atypical, Susceptibility To, 6

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

CFH, DGKE, CD46, C3, CFB, THBD, CFHR3, CFHR1, CFI, VTN, BAAT, ADAMTS13, TRIM25, C17orf67, CAPG, C5, CFHR5, VWF, C4BPA, C5AR1, IGAN1, PLG, C4BPB, CRP, GRHPR, CFHR4, C3AR1, TNF, GPR182, CABIN1

CFH, DGKE, CD46, C3, CFB, THBD, CFHR3, CFHR1, CFI, VTN, BAAT, ADAMTS13, TRIM25, C17orf67, CAPG, C5, CFHR5, VWF, C4BPA, C5AR1, IGAN1, PLG, C4BPB, CRP, GRHPR, CFHR4, C3AR1, TNF, GPR182, CABIN1, HPLH1, SMARCAL1, KRT20, SPZ1, PRSS55, CRISP2, THBS1, CRYGD, HP, ETFA, FHL1, MTOR, G6PD, GPI, CR1, CPB1, CD40LG, SPTA1, IL5, CD36, MUC1, MS4A1, NHS, PIGA, MASP1, NFE2L2

Drugs

Antagonist of the complement 5a receptor, Complement factor H, Eculizumab ( SOLIRIS )

Antagonist of the complement 5a receptor, Complement factor H, Eculizumab ( SOLIRIS ), Recombinant human minibody against complement component C5

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A number sign (#) is used with this entry because susceptibility to the development of atypical hemolytic uremic syndrome-6 (AHUS6) can be conferred by mutation in the gene encoding thrombomodulin (THBD; 188040).

For a general phenotypic description and a discussion of genetic heterogeneity of aHUS, see AHUS1 (235400).

Clinical Features

Delvaeye et al. (2009) reported 7 patients with atypical hemolytic uremic syndrome characterized by 1 or more episodes of microangiopathic hemolytic anemia and thrombocytopenia associated with acute renal failure. Four patients had decreased serum C3 (120700), consistent with activation of the alternative complement pathway. C4 (120810) levels were normal.

Molecular Genetics

In 7 (4.6%) of 153 patients with aHUS, Delvaeye et al. (2009) identified 6 different heterozygous mutations in the THBD gene (see, e.g., 188040.0005-188040.0008). In vitro functional expression studies showed that cells transfected with mutant THBD were less effective in converting C3b to iC3b on the cell surface after complement activation, and were thus not as well protected against complement activation. The findings indicated that mutations in the THBD gene contribute to the development of aHUS.