Early infantile onset of atypical hemolytic-uremic syndrome is caused by recessive mutations in DGKE

摘要

Atypical hemolytic-uremic syndrome (aHUS; MIM 615008) is a rare thrombotic disorder in the small vessels of the kidneys resulting in microangiopathic hemolytic anemia, thrombocytopenia and renal failure. Compared to the typical form of the disease (HUS), which is triggered by bacterial toxins and generally treated to full recovery, aHUS is caused by genetic or autoimmune factors. The familial form of aHUS also has a poor clinical prognosis with approximately 60% of patients progressing to end-stage renal disease and a mortality rate of 25%. (1) To date, mutations in nine genes (CFH, CFHR1/3/4, MCP, CFI, CFB, C3, THBD) involved in the complement system cascade are known to be associated with aHUS. The disease primarily affects children, but the penetrance, severity, treatment and short-term and long-term outcomes of the disorder depend on the underlying genetic mutation.