背景:婴儿肝功能衰竭综合征1型(ILFS1,OMIM#615,438),由亮氨酰-tRNA合酶1(LARS1,OMIM*151,350)缺陷引起,是一种罕见的常染色体隐性遗传疾病.临床表现,分子遗传特征,LARS1疾病的预后仍然难以捉摸。
方法:确定了三个新的ILFS1实例,在LARS1中具有确认的变异,编码LARS1。总结了疾病特征以及33例报告的病例。进行Kaplan-Meier分析以评估ILFS1患者的预后因素。
结果:3例新的ILFS1患者在LARS1中有6种新的变异。在36名已知患者中,12例死亡或接受肝移植。ILFS1的主要临床特征是宫内生长受限(31/32例患者对此进行了具体描述),未能茁壮成长(30/31),低蛋白血症(32/32),小细胞性贫血(32/33),急性肝功能衰竭(24/34),神经发育迟缓(25/30),缉获量(22/29),肌张力减退(13/27)。在基因型与肝衰竭的存在或疾病的临床严重程度之间没有观察到显着的相关性。Kaplan-Meier分析表明发病年龄<3mo(p=0.0015,风险比=12.29,95%置信区间[CI]=3.74-40.3),如肝功能衰竭(p=0.0343,风险比=6.57,95%CI=1.96-22.0),预后不良。
结论:介绍年龄较早,比如肝功能衰竭,导致ILFS1预后不良。基因型-表型相关性仍有待建立。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: Early age of presentation, like liver failure, confers poor prognosis in ILFS1. Genotype-phenotype correlations remain to be established.