PDF(Pubmed)
Abstract：
UNASSIGNED: Succinate dehydrogenase deficiency, also known as mitochondrial complex II deficiency, is a rare inborn error of metabolism, accounting for approximately 2% of mitochondrial disease. Mutations in the four genes SDHA, B, C,and D have been reported resulting in diverse clinical presentations. The vast majority of clinically affected individuals reported in the literature harbor genetic variants within the SDHA gene and present with a Leigh syndrome phenotype, clinically defined as a subacute necrotizing encephalopathy.
UNASSIGNED: Herein, we report the first case of a 7-year-old child who was diagnosed as having succinate dehydrogenase deficiency. The affected child presented at 1 year of age with encephalopathy and developmental regression following viral illnesses. MRI changes supported a clinical diagnosis of Leigh syndrome and c.1328C>Q and c.872A>C SDHA variants were identified as compound heterozygous. Mitochondrial cocktail treatment including L-carnitine, riboflavin, thiamine, biotin, and ubiquinone was started. Mild clinical improvement was observed after treatment. He is now unable to walk and speak. The second patient, a 21-year-old woman, presented with generalized muscle weakness, easy fatigability, and cardiomyopathy. Investigations revealed increased lactate level of 67.4 mg/dL (4.5-19.8) with repeatedly increased plasma alanine levels 1,272 µmol/L (200-579). We administered carnitine, coenzyme, riboflavin, and thiamine for empirical therapy with the suspicion of mitochondrial disease. Clinical exome sequencing revealed compound heterozygous variants NM_004168.4:c.1945_1946del (p.Leu649GlufsTer4) at exon 15 of the SDHA gene and NM_004168.4:c.1909-12_1909-11del at intron 14 of SDHA gene.
UNASSIGNED: There are several very different presentations including Leigh syndrome, epileptic encephalopathy, and cardiomyopathy. Some cases present following viral illness; this feature is not specific to mitochondrial complex II deficiency and occurs in many other mitochondrial disease presentations. There is no cure for complex II deficiency, though some reported patients showed clinical improvement following riboflavin therapy. Riboflavin is not the only therapeutic intervention that is available to patients with an isolated complex II deficiency and various other compounds have shown promise in the treatment of symptoms, including L-carnitine and ubiquinone. Treatment alternatives such as parabenzoquinone EPI-743 and rapamycin are under study in the treatment of the disease.
UNASSIGNED: Herein, we report the first case of a 7-year-old child who was diagnosed as having succinate dehydrogenase deficiency. The affected child presented at 1 year of age with encephalopathy and developmental regression following viral illnesses. MRI changes supported a clinical diagnosis of Leigh syndrome and c.1328C>Q and c.872A>C SDHA variants were identified as compound heterozygous. Mitochondrial cocktail treatment including L-carnitine, riboflavin, thiamine, biotin, and ubiquinone was started. Mild clinical improvement was observed after treatment. He is now unable to walk and speak. The second patient, a 21-year-old woman, presented with generalized muscle weakness, easy fatigability, and cardiomyopathy. Investigations revealed increased lactate level of 67.4 mg/dL (4.5-19.8) with repeatedly increased plasma alanine levels 1,272 µmol/L (200-579). We administered carnitine, coenzyme, riboflavin, and thiamine for empirical therapy with the suspicion of mitochondrial disease. Clinical exome sequencing revealed compound heterozygous variants NM_004168.4:c.1945_1946del (p.Leu649GlufsTer4) at exon 15 of the SDHA gene and NM_004168.4:c.1909-12_1909-11del at intron 14 of SDHA gene.
UNASSIGNED: There are several very different presentations including Leigh syndrome, epileptic encephalopathy, and cardiomyopathy. Some cases present following viral illness; this feature is not specific to mitochondrial complex II deficiency and occurs in many other mitochondrial disease presentations. There is no cure for complex II deficiency, though some reported patients showed clinical improvement following riboflavin therapy. Riboflavin is not the only therapeutic intervention that is available to patients with an isolated complex II deficiency and various other compounds have shown promise in the treatment of symptoms, including L-carnitine and ubiquinone. Treatment alternatives such as parabenzoquinone EPI-743 and rapamycin are under study in the treatment of the disease.
摘要：
■琥珀酸脱氢酶缺乏症，也被称为线粒体复合物II缺乏症，是一种罕见的先天代谢错误，约占线粒体疾病的2%。四个基因SDHA的突变，B,C,和D已被报道导致不同的临床表现。文献中报道的绝大多数临床受影响的个体在SDHA基因内具有遗传变异，并表现为Leigh综合征表型，临床定义为亚急性坏死性脑病。
■这里，我们报道了首例7岁儿童被诊断为琥珀酸脱氢酶缺乏症的病例.受影响的儿童在1岁时出现病毒性疾病后出现脑病和发育退化。MRI改变支持Leigh综合征的临床诊断,并且c.1328C>Q和c.872A>CSDHA变体被鉴定为复合杂合。线粒体鸡尾酒治疗，包括左旋肉碱，核黄素,硫胺素,生物素,泛醌开始了。治疗后临床症状轻度改善。他现在不能走路和说话。第二个病人,一个21岁的女人,表现为全身肌肉无力，容易疲劳,和心肌病。调查显示，乳酸水平升高67.4mg/dL（4.5-19.8），血浆丙氨酸水平反复升高1,272µmol/L（200-579）。我们服用了肉碱,辅酶,核黄素,和硫胺素用于经验性治疗，怀疑线粒体疾病。临床外显子组测序显示复合杂合变体NM_004168.4：c.1945_1946del（第Leu649GlufsTer4）在SDHA基因的外显子15处，NM_004168.4：c.1909-12_1909-11del在SDHA基因的内含子14处。
■有几种非常不同的介绍，包括Leigh综合征，癫痫性脑病,和心肌病。某些病例出现在病毒性疾病之后；此特征不是线粒体复合物II缺乏所特有的，并且发生在许多其他线粒体疾病表现中。复杂的II缺乏症没有治愈方法，尽管一些报告的患者在核黄素治疗后显示出临床改善。核黄素不是唯一的治疗干预，可用于患者的孤立的复杂II缺乏症和各种其他化合物已显示出希望在治疗症状，包括左旋肉碱和泛醌。正在研究治疗该疾病的替代方法，例如对苯醌EPI-743和雷帕霉素。
■这里，我们报道了首例7岁儿童被诊断为琥珀酸脱氢酶缺乏症的病例.受影响的儿童在1岁时出现病毒性疾病后出现脑病和发育退化。MRI改变支持Leigh综合征的临床诊断,并且c.1328C>Q和c.872A>CSDHA变体被鉴定为复合杂合。线粒体鸡尾酒治疗，包括左旋肉碱，核黄素,硫胺素,生物素,泛醌开始了。治疗后临床症状轻度改善。他现在不能走路和说话。第二个病人,一个21岁的女人,表现为全身肌肉无力，容易疲劳,和心肌病。调查显示，乳酸水平升高67.4mg/dL（4.5-19.8），血浆丙氨酸水平反复升高1,272µmol/L（200-579）。我们服用了肉碱,辅酶,核黄素,和硫胺素用于经验性治疗，怀疑线粒体疾病。临床外显子组测序显示复合杂合变体NM_004168.4：c.1945_1946del（第Leu649GlufsTer4）在SDHA基因的外显子15处，NM_004168.4：c.1909-12_1909-11del在SDHA基因的内含子14处。
■有几种非常不同的介绍，包括Leigh综合征，癫痫性脑病,和心肌病。某些病例出现在病毒性疾病之后；此特征不是线粒体复合物II缺乏所特有的，并且发生在许多其他线粒体疾病表现中。复杂的II缺乏症没有治愈方法，尽管一些报告的患者在核黄素治疗后显示出临床改善。核黄素不是唯一的治疗干预，可用于患者的孤立的复杂II缺乏症和各种其他化合物已显示出希望在治疗症状，包括左旋肉碱和泛醌。正在研究治疗该疾病的替代方法，例如对苯醌EPI-743和雷帕霉素。
