CFH gene mutation in a case of Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS)

We report the case of a patient with Shiga toxin (Stx)-associated hemolytic-uremic syndrome (HUS) (STEC-HUS) with a concomitant heterozygous mutation of the gene coding for complement Factor H (CFH).

An 18-month-old patient presented with hemolytic anemia and thrombotic microangiopathy in the context of acute gastroenteritis. While the patient did not show kidney or other organ failure, he had persistent hemolysis and complement 3 activation (low C3), leading to the decision to commence immunotherapy with eculizumab (Soliris®) together with transient antibiotic coverage and meningococcal vaccination. Patient outcome was favorable. Diagnostic work-up identified Escherichia coli-associated Type 2 Shiga toxin. Complement analysis showed a heterozygous mutation of the CFH gene (c.2103 G>A, p. Trp701X) resulting in a quantitative CFH defect.

We report a case of STEC-HUS with a quantitative CFH defect caused by a mutation of the CFH gene. To the best of our knowledge, very few cases of STEC-HUS with complement gene mutation have been reported, but none to date with a CFH mutation. We therefore suggest that complement analyses be performed in patients diagnosed with STEC-HUS in association with low C3 levels, especially in patients presenting with severe or unexpected clinical symptoms.