Holme E, Greter J, Jacobson C E, Larsson N G, Lindstedt S, Nilsson K O, Oldfors A, Tulinius M
Department of Clinical Chemistry, University of Gothenburg, Sahlgren's Hospital, Sweden.
Pediatr Res. 1992 Dec;32(6):731-5. doi: 10.1203/00006450-199212000-00022.
We report the finding of mitochondrial ATP-synthase deficiency in a child with persistent 3-methylglutaconic aciduria. The child presented in the neonatal period with severe lactic acidosis, which was controlled by Na-HCO3 and glucose infusions. During the 1st y of life, there were several episodes of lactic acidosis precipitated by infections or prolonged intervals between meals. The excretion of lactate in urine was variable, but there was a persistent high excretion of 3-methylglutaconic acid. The activity of 3-methylglutaconyl-CoA hydratase in fibroblasts was normal. The child had a hypertrophic cardiomyopathy and magnetic resonance images revealed hypoplasia of corpus callosum. The gross motor and mental development was retarded, but there were no other neurologic signs. Investigation of muscle mitochondrial function at 1 y of age revealed a severe mitochondrial ATP-synthase deficiency (oligomycin-sensitive, dinitrophenol-stimulated Mg2+ ATPase activity: 27 nmol x min-1 x (mg protein)-1, control range 223-673 nmol x min-1 x (mg protein)-1. The mitochondrial respiratory rate was low and tightly coupled. The respiratory rate was normalized by the addition of an uncoupler. Low Mg2+ ATPase activity was also demonstrated by histochemical methods. Morphologic examination revealed ultrastructural abnormalities of mitochondria. There was no deletion of mitochondrial DNA. The sequences of the ATP synthase subunit genes of mitochondrial DNA were in accordance with published normal sequences.
我们报告了一名患有持续性3-甲基戊二酸尿症的儿童线粒体ATP合酶缺乏的发现。该儿童在新生儿期出现严重乳酸酸中毒，通过输注碳酸氢钠和葡萄糖得以控制。在1岁以内，因感染或进食间隔延长曾发生过几次乳酸酸中毒发作。尿中乳酸排泄量变化不定，但3-甲基戊二酸排泄持续偏高。成纤维细胞中3-甲基戊二酰辅酶A水合酶活性正常。该儿童患有肥厚型心肌病，磁共振成像显示胼胝体发育不全。粗大运动和智力发育迟缓，但无其他神经学体征。1岁时对肌肉线粒体功能的研究显示严重的线粒体ATP合酶缺乏（寡霉素敏感、二硝基酚刺激的Mg2+ATP酶活性：27 nmol·min-1·(mg蛋白质)-1，对照范围223 - 673 nmol·min-1·(mg蛋白质)-1）。线粒体呼吸率低且紧密偶联。加入解偶联剂后呼吸率恢复正常。组织化学方法也证实了Mg2+ATP酶活性低。形态学检查显示线粒体超微结构异常。线粒体DNA无缺失。线粒体DNA的ATP合酶亚基基因序列与已发表的正常序列一致。
