Severe course with lethal hepatocellular injury and skeletal muscular dysgenesis in a neonate with infantile liver failure syndrome type 1 caused by novel LARS1 mutations

Katsuya Hirata, Nobuhiko Okamoto, Chihiro Ichikawa, Shouta Inoue, Masatoshi Nozaki, Kimihiko Banno, Toshiki Takenouchi, Hisato Suzuki, Kenjiro Kosaki

Research output: Contribution to journalArticlepeer-review

Abstract

Infantile liver failure syndrome type 1 (ILFS1) is a recently recognized autosomal recessive disorder caused by deleterious mutations in the leucyl-tRNA synthetase 1 gene (LARS1). The LARS1 enzyme is responsible for incorporation of the amino acid leucine during protein polypeptide synthesis. Individuals with LARS1 mutations typically show liver failure from infancy to early childhood during periods of illness or other physiological stress. While 25 patients from 15 families with ILFS1 have been reported in the literature, histological reports from autopsy findings are limited. We report here a premature male neonate who presented with severe intrauterine growth retardation, microcytic anemia, and fulminant liver failure, and who was a compound heterozygote for two novel deleterious mutations in LARS1. An autopsy showed fulminant hepatitis-like hepatocellular injury and fibrogenesis in the liver and a lack of uniformity in skeletal muscle, accompanied by the disruption of striated muscle fibers. Striking dysgenesis in skeletal muscle detected in the present case indicates the effect of LARS1 functional deficiency on the musculature. Whole-exome sequencing may be useful for neonates with unexplained early liver failure if extensive genetic and metabolic testing is inconclusive.

Original languageEnglish
Pages (from-to)866-870
Number of pages5
JournalAmerican Journal of Medical Genetics, Part A
Volume185
Issue number3
DOIs
Publication statusPublished - 2021 Mar

Keywords

  • LARS
  • extremely low birth weight infant
  • intrauterine growth retardation
  • neonatal acute liver failure
  • tRNA synthetase deficiency

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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