Succinyl-CoA Ligase Deficiency: A Mitochondrial Hepatoencephalomyopathy
Succinyl-CoA Ligase Deficiency: A Mitochondrial Hepatoencephalomyopathy
复制标题
DOI：
10.1203/00006450-201011001-00310
复制
发表时间：
2010-08-01
影响因子：
3.6
通讯作者：
Waterham, Hans R.
中科院分区：
文献类型：
--
作者：
Van Hove, Johan L. K.;Saenz, Margarita S.;Waterham, Hans R.
患者出生后第一天出现明显的乳酸酸中毒，并伴有乳酸/丙酮酸比值升高。尿有机酸呈Krebs循环代谢物，甲基丙二酸甲酯和柠檬酸甲酯轻度升高。酰卡尼汀图谱显示丙酰卡尼汀和琥珀酰卡尼汀升高。氨基酸表现为谷氨酸、谷氨酰胺、脯氨酸和丙氨酸升高。从2岁开始，她就出现转氨酶升高和间歇性肝功能衰竭。肝脏活检显示脂肪变性，线粒体DNA减少到对照组的50%。她有双侧感音神经性听力损失。在出生后的头两年，她患上了进行性严重的肌病，并伴有明显的肌肉无力，最终导致呼吸衰竭、利氏病和反复发生的肝功能衰竭。天冬氨酸治疗后肝脏症状和代谢参数暂时改善，但肌肉症状和脑损害均未改善。实验室检测发现成纤维细胞琥珀酰辅酶A连接酶活性和蛋白缺乏，这是由于SUCLG1基因的一种新的纯合子突变：C.40A>；T(p.M14L)。功能分析表明，这种蛋氨酸更有可能作为翻译启动子蛋氨酸发挥作用，解释了突变的致病性质。由SUCLG1突变引起的琥珀酰辅酶A连接酶缺陷是线粒体肝脑肌病的新原因。(儿科研究报告68：159-164,2010)
This patient presented on the first day of life with pronounced lactic acidosis with an elevated lactate/pyruvate ratio. Urine organic acids showed Krebs cycle metabolites and mildly elevated methylmalonate and methylcitrate. The acylcarnitine profile showed elevated propionylcarnitine and succinylcarnitine. Amino acids showed elevated glutamic acid, glutamine, proline, and alanine. From the age 2 of mo on, she had elevated transaminases and intermittent episodes of liver failure. Liver biopsy showed steatosis and a decrease of mitochondrial DNA to 50% of control. She had bilateral sensorineural hearing loss. Over the course of the first 2 y of life, she developed a progressively severe myopathy with pronounced muscle weakness eventually leading to respiratory failure, Leigh disease, and recurrent hepatic failure. The hepatic symptoms and the metabolic parameters temporarily improved on treatment with aspartate, but neither muscle symptoms nor brain lesions improved. Laboratory testing revealed a deficiency of succinyl-CoA ligase enzyme activity and protein in fibroblasts because of a novel homozygous mutation in the SUCLG1 gene: c.40A>T (p.M14L). Functional analysis suggests that this methionine is more likely to function as the translation initiator methionine, explaining the pathogenic nature of the mutation. Succinyl-CoA ligase deficiency due to an SUCLG1 mutation is a new cause for mitochondrial hepatoencephalomyopathy. (Pediatr Res 68: 159-164, 2010)