Table 1.
Atypical hemolytic uremic syndrome: genetic contributions, clinical presentations and risk of discontinuation of eculizumab.
| Genes | Chr. locus | Proteins | Proportion to atypical HUS | Clinical presentations | Risk of disconti of eculizumab14 |
|---|---|---|---|---|---|
| C3 | 19p13.3 | Complement C3 | 2-8%15 | Typically present in childhood, 60% develop ESRD. 57% response to plasma exchange6 | High16 |
| CD46 | 1q32.2 | Membrane cofactor protein | 5-9%15,17 | Typically present in childhood, milder acute episode. 80% complete remission, 60-70% of individuals remain dialysis free even after several recurrences6 | Low |
| CFB | 6p21.33 | Complement factor B | Rare15,18 | Presenting both in childhood and adulthood. Higher variability. 70% eventually ESRD19 | |
| CFH | 1q31.3 | Complement factor H | 21-22%15 | High risk of relapse, 60-80% ESRD or death. Liver-kidney transplantation20 | High21 |
| CFHR1-5 | 1q31.3 | Complement factor H-related protein 1 | CFHR3/CFHR1 deletion: 28%22 CFH/CFHR1 hybrid: 3-5% CFRH1/CFHR4 deletion: rare | Poor clinical prognosis and high risk of post-transplant recurrence23-25 | Low for homozygous CFHR3/CFHR1 deletion |
| CFI | 4q25 | Complement factor I, C3b inactivator | 4-8%15 | Variable. 58% ESRD6 | Low |
| DGKE | 17q22 | Diacylglycerol kinase epsilon | ~27% of those present at age <1 year | Onset before 1-year old in homozygote patient.26 Early chronic kidney disease | |
| THBD | 20p11.21 | Thrombomodulin | ~5% | 90% present in childhood. 50% ESRD. Plasma treatment induced disease remission in about 80% of acute episodes6 | |
| CFH auto-antibody | Highly relapsing disease course. Significant gastrointestinal symptoms and/or diarrhea, thus, resembling eHUS. May have infection trigger.27 Plasma exchange and immunosuppression therapy28 |