线粒体 DNA 缺失综合征 13。病例报告

G. Golosnaya, O. N. Krasnorutskaya, N. A. Ermolenko, V. L. Efimova, T. A. Larionova, D. M. Subbotin, D. A. Feklistov, M. D. Tysyachina
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引用次数: 0

摘要

出生时宫内肌张力低下和发育迟缓儿童脑瘫的病因通常是宫内慢性缺氧。然而,肌肉张力低下和发育迟缓的患儿需要进行遗传学检查。本研究旨在报告一例由 FBXL4 基因突变引起的线粒体疾病,并确定幼儿期线粒体 DNA(mtDNA)缺失综合征(MDS)的主要诊断标准。线粒体DNA缺失综合征-13与位于6q16.1-q16.27位点的FBXL4基因突变有关。这种疾病由 P.E. Bonnen 和 X. Gai 于 2013 年首次独立描述。MDS是一组临床和遗传异质性疾病,为常染色体隐性遗传,由支持mtDNA生物发生和完整性的基因突变引起。脑肌病 mtDNA 缺失综合征-13(MTDPS13)(OMIM: 615471)是一种极其罕见的常染色体隐性遗传病,由 FBXL4 基因(MIM: 605654)的双偶联突变引起,估计发病率为每 10 万至 40 万新生儿中 1 例。该病通常在新生儿期发病,75% 的患者在 3 个月大时出现症状。在大多数病例中,mtDNA缺失综合征-13 在新生儿早期就已出现症状;但也有一些患者在 24 个月大时才发病。该病的特征是脑病、低血压、乳酸酸中毒、严重发育迟缓以及脑磁共振成像显示的基底节区域的变化。FBXL4 相关脑肌病是一种多系统疾病,主要影响中枢神经系统、心脏和肝脏。它有不同的临床表现,如乳酸酸中毒、发育迟缓、全身性低血压、营养失调和生长迟缓。有些患者会表现出特殊的面部特征,包括前额突出、窦状皱褶、浓眉、长睫毛、上睑下垂、眼裂短、肥大、鼻梁宽而下陷、唇沟长而光滑、上唇薄和耳朵低垂。该病的预后极差,大多数患儿在 4 岁前死亡。约半数患者患有小头畸形和高氨血症。结果各不相同;据报告,30%的病例死亡。平均死亡时间为 3 年(中位数为 2 年)。诊断对医疗和遗传咨询以及可能的产前诊断至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mitochondrial DNA depletion syndrome 13. A case report
The etiology of cerebral palsy in children with intrauterine hypotrophy at birth and developmental delay is often explained by chronic intrauterine hypoxia. However, children with muscle hypotonia and developmental delay require genetic examination. The aim of this study is to report a case of mitochondrial disease caused by FBXL4 gene mutations and to identify main diagnostic criteria for mitochondrial DNA (mtDNA) depletion syndromes (MDS) in early childhood. Mitochondrial DNA depletion syndrome-13 is associated with FBXL4 gene mutations located in the 6q16.1–q16.27 locus. This disorder was first described in 2013 by P.E. Bonnen and X. Gai independently. MDS are a clinically and genetically heterogeneous group of diseases inherited by an autosomal recessive type and caused by mutations in genes that support the biogenesis and integrity of mtDNA. Encephalomyopathic mtDNA depletion syndrome-13 (MTDPS13) (OMIM: 615471) is an exceedingly rare autosomal recessive disease caused by biallelic mutations in the FBXL4 gene (MIM: 605654) with an estimated prevalence of 1 case per 100,000– 400,000 newborns. The disease onset is usually observed in the neonatal period; 75 % of patients develop symptoms by the age of 3 months. In the majority of cases, mtDNA depletion syndrome-13 manifests itself in the early neonatal period; however, in some patients, the disease onset was registered by the age of 24 months. The disease is characterized by encephalopathy, hypotension, lactic acidosis, severe developmental delay, and changes in the area of basal ganglia revealed by magnetic resonance imaging of the brain. FBXL4-related encephalomyopathy is a multisystem disease primarily affecting the central nervous system, heart, and liver. It is characterized by different clinical manifestations such as lactic acidosis, developmental delay, generalized hypotension, nutritional disorders, and growth retardation. Some patients demonstrate specific facial features, including prominent forehead, sinus-shaped folds, thick eyebrows, long eyelashes, epicanthus, short eye slits, hypertelorism, wide and depressed nose bridge, long and smooth labial groove, thin upper lip, and low-set ears. The disease prognosis is extremely poor; most children die before the age of 4 years. Approximately half of the patients suffer from microcephaly and hyperammonemia. The outcome varies; death was reported in 30 % of cases. Mean time to death was 3 years (median – 2 years). The diagnosis is crucial for medical and genetic counseling and possible prenatal diagnosis.
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