Severe neonatal manifestations of infantile liver failure syndrome type 1 caused by cytosolic leucine-tRNA synthetase deficiency

Christina Peroutka, Jacqueline Salas, Jacquelyn Britton, Juliet Bishop, Lisa Kratz, Maureen Gilmore, Jill Ann Fahrner, W Christopher Golden, Tao Wang

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Background: Deleterious mutations in cytosolic leucine-tRNA synthetase (LARS) cause infantile liver failure syndrome, type 1 (ILFS1), a recently recognized, rare autosomal recessive disorder (OMIM151350). Only six families with ILFS1 have been reported in the literature. Patients with ILFS1 are typically diagnosed between 5 and 24 months of age with failure to thrive, developmental delays, encephalopathy, microcytic anemia, and chronic liver dysfunction with recurrent exacerbations following childhood illnesses. Neonatal manifestations of this disorder have not been well documented. Case Report: We report a premature female newborn with intrauterine growth restriction, failure to thrive, congenital anemia, anasarca, and fulminant liver failure leading to lethal multiple organ failure. Liver failure in this infant was characterized by a disproportionate impairment of liver synthetic function, including severe coagulopathy and hypoalbuminemia without significant defects in liver detoxification or evidence of hepatocellular injury during early phase of the disease. Whole-exome sequencing of child-parent trio identified two inherited missense mutations in LARS in this patient. One, c.1292T>A; p.Val431Asp, has been reported in patients with ILFS1, while the other, c.725C>T; p.Pro242Leu, is novel. Both mutations involve amino acid residues in the highly conserved editing domain of LARS, are predicted to be functionally deleterious, and presumably contribute to the clinical manifestations in this patient. Conclusion: This is the first case documenting neonatal manifestation of ILFS1, highlighting early, severe, and disproportionate defects in liver synthetic function. Timely diagnosis of ILFS1 is crucial to guide critical clinical management and improve outcomes of this rare and potentially life-threatening disorder.

Original languageEnglish (US)
Title of host publicationJIMD Reports
PublisherSpringer
Pages71-76
Number of pages6
DOIs
StatePublished - Jan 1 2019

Publication series

NameJIMD Reports
Volume45
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Keywords

  • Fulminant liver failure
  • Infantile liver failure syndrome 1
  • Leucine-tRNA synthetase
  • Mutations
  • Neonate

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)

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