Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1.
LARS1
acute liver failure
aminoacyl-tRNA synthetase deficiency
infantile liver failure syndrome type 1
metabolic stroke
Journal
Genetics in medicine : official journal of the American College of Medical Genetics
ISSN: 1530-0366
Titre abrégé: Genet Med
Pays: United States
ID NLM: 9815831
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
14
01
2020
accepted:
30
06
2020
revised:
29
06
2020
pubmed:
24
7
2020
medline:
29
4
2021
entrez:
24
7
2020
Statut:
ppublish
Résumé
Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke.
Identifiants
pubmed: 32699352
doi: 10.1038/s41436-020-0904-4
pii: S1098-3600(21)00788-7
doi:
Types de publication
Journal Article
Multicenter Study
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1863-1873Subventions
Organisme : NINDS NIH HHS
ID : R35 NS105078
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG006542
Pays : United States
Organisme : NHGRI NIH HHS
ID : K08 HG008986
Pays : United States
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