Recurrent acute liver failure in alanyl-tRNA synthetase-1 (AARS1) deficiency

Lara M Marten; Florian Brinkert; Desirée E C Smith; Holger Prokisch; Maja Hempel; René Santer

doi:10.1016/j.ymgmr.2020.100681

Recurrent acute liver failure in alanyl-tRNA synthetase-1 (AARS1) deficiency

Mol Genet Metab Rep. 2020 Nov 22:25:100681. doi: 10.1016/j.ymgmr.2020.100681. eCollection 2020 Dec.

Authors

Lara M Marten¹, Florian Brinkert¹, Desirée E C Smith², Holger Prokisch³, Maja Hempel⁴, René Santer¹

Affiliations

¹ Department of Pediatrics, University Medical Center Eppendorf, Hamburg, Germany.
² Department of Clinical Chemistry, Amsterdam University Medical Centers, Amsterdam, the Netherlands.
³ Institute of Human Genetics, Technical University Munich, Munich, Germany.
⁴ Institute of Human Genetics, University Medical Center Eppendorf, Hamburg, Germany.

Abstract

AARS1 deficiency belongs to the group of disorders affecting aminoacyl-tRNA synthetases. To date, AARS1 deficiency has only been linked to neurologic disorders. We report a 6-year-old girl with microcephaly and developmental delay who presented with repeated episodes of acute liver failure. Whole-exome sequencing revealed compound heterozygosity for two missense variants within the AARS1 gene, p.[Leu298Gln];[Arg751Gly]), whose functional relevance was demonstrated by decreased enzymatic activity in fibroblasts. This is the first report that shows that AARS1 variants may be associated with recurrent acute liver failure.

Keywords: AARS1; AARS1, alanyl-(aminoacyl)-tRNA synthetase-1; Aminoacylation; Metabolic disease; PICU, pediatric intensive care unit; Protein biosynthesis; Recurrent acute liver failure; aaRS, aminoacyl-tRNA synthetase; mtDNA, mitochondrial DNA; nDNA, nuclear DNA.