Comprehensive gene profiling by Next-Generation sequencing in a cohort of Egyptian pediatric Atypical HUS

Atypical hemolytic uremic syndrome (aHUS) is a rare, severe condition in children, resulting from uncontrolled complement activation caused by genetic factors or autoantibodies; it usually has a poor prognosis. Early identification of the underlying genetic variants is crucial for guiding management and predicting outcomes. This study aimed to identify gene mutations in Egyptian children with aHUS at an early stage. This would enable the selection of the most appropriate treatment options and help prevent adverse outcomes for the patients.

This is an observational cohort study, included 21 children with a clinical diagnosis of aHUS who presented to the Pediatric Nephrology Unit and general wards of Cairo University Children's Hospital between June 2022 and January 2024 with a follow-up duration of 12 months (median). All patients underwent whole exome sequencing (WES). Clinical data, treatment regimens, and outcomes were recorded and analyzed.

Among the 21 patients, around one third had negative WES results while 28.57 % showed CFHR 3/CFHR1 deletion. Most patients progressed to chronic kidney disease (52.4 %), while 28.6 % recovered their kidney functions following plasmapheresis. A significant association was observed between WES category and disease relapse (p = 0.021); patients with CFHR3 deletion, CFHR5 deletion, or MMUT variant developed at least one attack of relapse.

Egyptian children with aHUS demonstrate marked genetic heterogeneity. A substantial proportion lacked identifiable pathogenic variants, highlighting the complexity of the disease. CFHR3/CFHR1 deletion was the most frequent finding. Genetic profiling remains crucial for anticipating relapse risk and guiding therapeutic decisions, particularly in resource-limited settings.