Atypical haemolytic uraemic syndrome is an ultra-rare, life-threatening disease. Causative
variants in genes that encode complement factors can be identified in 40-70% of cases.
We performed genetic analysis of 21 Czech children with atypical haemolytic uraemic
syndrome. Genetic or acquired predisposition to the disease was identified in the
majority of our patients: CFHR1 and CFHR3 deletions in 14/21 (67%; 13 of them were
positive for anti-complement factor H antibodies), variants in complement genes or
DGKE in 13/21 (62%). Multiple genetic findings were identified in eight patients (38%).
The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population
was estimated to be 0.092 (CI 0.053-0.131) cases per million inhabitants and 0.92
(CI 0.53-1.32) cases per 100,000 births for the entire reporting period. Ten patients
were initially treated with plasma exchange and eight with eculizumab or with a combination
of eculizumab and plasma exchange. At the last follow-up, 20 patients were alive and
one patient had end-stage renal disease.Conclusion: The incidence of atypical haemolytic
uraemic syndrome in the Czech paediatric population corresponds to the reported incidence
in Europe. We detected the unusually high rate of CFHR1/CFHR3 deletions associated
with anti-complement factor H antibodies in Czech paediatric patients. Treatment by
eculizumab led to superior outcomes and prevention of the disease relapses compared
with plasma exchange therapy. Our results may help to understand the polygenic nature
of atypical haemolytic uraemic syndrome as a disease that results from a combination
of various risk factors.What is Known: • Atypical haemolytic uraemic syndrome (aHUS)
is considered a polygenic and multifactorial disease. Genetic predisposition to aHUS
is identified in 40-70% of children. • Anti-complement factor H antibodies are usually
found in 6-25% of affected children.What is New: • Potentially causative genetic or
acquired factors were confirmed in the majority of patients. The prevailing finding
was the unusually high rate of CFHR1/CFHR3 deletions associated with anti-complement
factor H antibodies (62% of patients). • The incidence of aHUS in Czech children is
0.092 (CI 0.053-0.131) cases per million inhabitants and 0.92 (CI 0.53-1.32) cases
per 100,000 births for the entire reporting period.
