
PMID- 35522339
OWN - NLM
STAT- MEDLINE
DCOM- 20220923
LR  - 20240903
IS  - 1432-198X (Electronic)
IS  - 0931-041X (Print)
IS  - 0931-041X (Linking)
VI  - 37
IP  - 11
DP  - 2022 Nov
TI  - Atypical hemolytic uremic syndrome induced by SARS-CoV2 infection in infants with 
      EXOSC3 mutation.
PG  - 2781-2784
LID - 10.1007/s00467-022-05566-6 [doi]
AB  - 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.
CI  - (c) 2022. The Author(s), under exclusive licence to International Pediatric 
      Nephrology Association.
FAU - Van Quekelberghe, Chantal
AU  - Van Quekelberghe C
AUID- ORCID: 0000-0002-9901-0852
AD  - Clementine Kinderhospital, Theobald-Christ-Strasse 16, 60316, Frankfurt am Main, 
      Germany. c.vanquekelberghe@ckhf.de.
FAU - Latta, Kay
AU  - Latta K
AD  - Clementine Kinderhospital, Theobald-Christ-Strasse 16, 60316, Frankfurt am Main, 
      Germany.
FAU - Kunzmann, Steffen
AU  - Kunzmann S
AD  - Burgerhospital, Frankfurt am Main, Germany.
FAU - Grohmann, Maik
AU  - Grohmann M
AD  - Medizinische Genetik Mainz, Mainz, Germany.
FAU - Hansen, Matthias
AU  - Hansen M
AD  - Clementine Kinderhospital, Theobald-Christ-Strasse 16, 60316, Frankfurt am Main, 
      Germany.
LA  - eng
PT  - Journal Article
DEP - 20220506
PL  - Germany
TA  - Pediatr Nephrol
JT  - Pediatric nephrology (Berlin, Germany)
JID - 8708728
RN  - 0 (EXOSC3 protein, human)
RN  - 0 (RNA, Viral)
RN  - 0 (RNA-Binding Proteins)
RN  - 9007-36-7 (Complement System Proteins)
RN  - EC 3.1.- (Exosome Multienzyme Ribonuclease Complex)
SB  - IM
MH  - *Atypical Hemolytic Uremic Syndrome/therapy
MH  - *COVID-19/complications
MH  - Complement System Proteins
MH  - Exosome Multienzyme Ribonuclease Complex/genetics
MH  - Humans
MH  - Infant
MH  - Mutation
MH  - *Neurodegenerative Diseases/complications
MH  - RNA, Viral
MH  - RNA-Binding Proteins/genetics
MH  - SARS-CoV-2
MH  - *Thrombotic Microangiopathies/complications/genetics
PMC - PMC9072151
OTO - NOTNLM
OT  - COVID-19
OT  - EXOSC3 mutation
OT  - RNA exosome
OT  - aHUS
COIS- No funding was received to assist with the preparation of this manuscript. The 
      authors have no competing interests to declare that are relevant to the content 
      of this article.
EDAT- 2022/05/07 06:00
MHDA- 2022/09/24 06:00
PMCR- 2022/05/06
CRDT- 2022/05/06 11:36
PHST- 2021/11/20 00:00 [received]
PHST- 2022/03/28 00:00 [accepted]
PHST- 2022/03/26 00:00 [revised]
PHST- 2022/05/07 06:00 [pubmed]
PHST- 2022/09/24 06:00 [medline]
PHST- 2022/05/06 11:36 [entrez]
PHST- 2022/05/06 00:00 [pmc-release]
AID - 10.1007/s00467-022-05566-6 [pii]
AID - 5566 [pii]
AID - 10.1007/s00467-022-05566-6 [doi]
PST - ppublish
SO  - Pediatr Nephrol. 2022 Nov;37(11):2781-2784. doi: 10.1007/s00467-022-05566-6. Epub 
      2022 May 6.
