Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by systemic thrombotic microangiopathy mainly in the kidneys and mostly due to genetic disorders leading to uncontrolled activation of the complement system. Severe complications of SARS-CoV2 infection are linked to microvascular injury and complement activation is suspected to play a role in the pathogenesis of endothelial cell damage in severe COVID-19.
Methods: We present the first two cases of aHUS triggered by SARS-CoV-2 infection in two unrelated infants with the same mutation in the RNA exosome gene EXOSC3. This mutation is known to cause pontocerebellar hypoplasia type 1b, an autosomal-recessive neurodegenerative disease. So far, no kidney involvement in affected persons was reported.
Results: As eculizumab treatment was unsuccessful and complement-mediated disorders were ruled out, we suppose that the atypical HUS in our two patients is not due to complement-mediated thrombotic microangiopathy but rather due to a dysfunction of the RNA exosome.
Conclusions: The RNA exosome is crucial for the precise processing and degradation of nuclear and cytoplasmatic RNA. We suspect that the SARS-CoV-2 infection led to changes in RNA that could not be offset by the defective RNA exosome in our two patients. The accumulation/wrong processing of the viral RNA must have led to the endothelial cell damage resulting in aHUS. This would be a new - "RNA-induced" - mechanism of aHUS.
Keywords: COVID-19; EXOSC3 mutation; RNA exosome; aHUS.
© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.