PDF(Pubmed)
Abstract：
One of the most common inborn errors in fatty acid β oxidation (FAO) is a very long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency. It is autosomal recessive. The enzyme used in the first phase of FAO is VLCAD. The enzyme is responsible for β oxidation spiral pathway\'s initial step, the dehydrogenation process of long-chain fatty acyl-CoA. The phenotypes include hypoglycemia, hepatomegaly, cardiomyopathy, and occasionally abrupt mortality. Most VLCAD deficiencies in newborns are now detected during the neonatal period due to the development of newborn screening programs. Mitochondrial DNA depletion syndromes (MTDPS) are one of the rarest metabolic disorders. It is an autosomal recessive disease caused by defects in genes necessary for the maintenance of mitochondrial DNA (mtDNA). One of these FBXL4 (F-box and leucine-rich repeat protein 4) variants causes encephalomyopathic mtDNA depletion syndrome 13 (MTDPS13), which presents as a failure to thrive, severe global developmental delay, hypotonia, early infantile onset of encephalopathy, and lactic acidosis. We report here the case of a Saudi infant born to consanguineous parents who presented to us with severe failure to thrive, profound neurodevelopmental delays, and facial dysmorphic features. Whole-exome sequencing (WES) showed the infants had MTDPS13. The FBXL4 variant c.1698A > G p. (Ile566Met) has previously been described as a disease that causes developmental delay and lactic acidosis, and another variant has also been detected in the patient. The ACADVL variant c.134C > A p. (Ser45*) has previously been described to cause VLCAD deficiency. A comprehensive literature review showed our patient to be the first case of MTDPS13 and VLCAD reported to date worldwide.
摘要：
脂肪酸β氧化（FAO）中最常见的先天性错误之一是非常长链的酰基辅酶A脱氢酶（VLCAD）缺乏症。它是常染色体隐性遗传。FAO第一阶段使用的酶是VLCAD。该酶负责β氧化螺旋途径的初始步骤，长链脂肪酰辅酶A的脱氢过程。表型包括低血糖，肝肿大,心肌病,偶尔会突然死亡。由于新生儿筛查计划的发展，新生儿的大多数VLCAD缺陷现在都是在新生儿期发现的。线粒体DNA耗竭综合征(MTDPS)是最罕见的代谢紊乱之一。它是一种常染色体隐性遗传疾病，由维持线粒体DNA（mtDNA）所必需的基因缺陷引起。其中一个FBXL4（F-box和富含亮氨酸的重复蛋白4）变异导致脑肌病mtDNA耗竭综合征13（MTDPS13），表现为未能茁壮成长，严重的全球发育迟缓，低张力,早期婴儿脑病发作，和乳酸性酸中毒.我们在这里报道了一个沙特婴儿的案例，该婴儿由近亲父母出生，他们给我们带来了严重的未能茁壮成长的情况，严重的神经发育迟缓,和面部畸形特征。全外显子组测序（WES）显示婴儿患有MTDPS13。FBXL4变体c.1698A>Gp。（Ile566Met）先前已被描述为导致发育迟缓和乳酸性酸中毒的疾病，在病人身上也发现了另一种变异。先前已经描述了ACADVL变体c.134C>Ap.(Ser45*)导致VLCAD缺乏。综合文献综述显示，我们的患者是迄今为止全球报道的第一例MTDPS13和VLCAD。
