%0 Journal Article
%T Early onset and liver failure indicating poor prognosis of infant liver failure syndrome type 1.
%A Li SY
%A Feng JY
%A Li ZD
%A Liu T
%J Orphanet J Rare Dis
%V 19
%N 1
%D 2024 Jun 6
%M 38844943
%F 4.303
%R 10.1186/s13023-024-03229-3
%X <B>BACKGROUND: </B>Infantile liver failure syndrome type 1 (ILFS1, OMIM #615,438), caused by leucyl-tRNA synthase 1 (LARS1, OMIM *151,350) deficiency, is a rare autosomal-recessive disorder. The clinical manifestations, molecular-genetic features, and prognosis of LARS1 disease remain largely elusive.<BR><B>METHODS: </B>Three new instances of ILFS1 with confirmed variants in LARS1, encoding LARS1, were identified. Disease characteristics were summarized together with those of 33 reported cases. Kaplan-Meier analysis was performed to assess prognostic factors in ILFS1 patients.<BR><B>RESULTS: </B>The 3 new ILFS1 patients harbored 6 novel variants in LARS1. Among the 36 known patients, 12 died or underwent liver transplantation. The main clinical features of ILFS1 were intrauterine growth restriction (31/32 patients in whom this finding was specifically described), failure to thrive (30/31), hypoalbuminemia (32/32), microcytic anemia (32/33), acute liver failure (24/34), neurodevelopmental delay (25/30), seizures (22/29), and muscular hypotonia (13/27). No significant correlations were observed between genotype and either presence of liver failure or clinical severity of disease. Kaplan-Meier analysis indicated that age of onset < 3mo (p = 0.0015, hazard ratio = 12.29, 95% confidence interval [CI] = 3.74-40.3), like liver failure (p = 0.0343, hazard ratio = 6.57, 95% CI = 1.96-22.0), conferred poor prognosis.<BR><B>CONCLUSIONS: </B>Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.