Rustin P, Lebidois J, Chretien D, Bourgeron T, Piechaud J F, Rötig A, Munnich A, Sidi D
Département de Pédiatrie, INSERM U-12, Hôpital des Enfants-Malades, Paris, France.
J Pediatr. 1994 Feb;124(2):224-8. doi: 10.1016/s0022-3476(94)70308-6.
Considering the high proportion of unexplained hypertrophic cardiomyopathies on the one hand and the occurrence of cardiomyopathies in several mitochondrial disorders on the other, we hypothesized that isolated hypertrophic cardiomyopathies in infancy could occasionally be the result of defects of oxidative phosphorylation. By means of a scaled-down technique, we were able to investigate oxidative phosphorylation on minute amounts of endomyocardial tissue (1 mg) in three patients with concentric hypertrophic cardiomyopathy (shortening fraction in diameter, 18% to 27%; normal mean +/- 1 SD, 33 +/- 3%) and in control subjects. Although the absolute respiratory chain enzyme activities in the endomyocardial biopsy specimens of the patients were within the low normal range, the determination of the activity ratios allowed us to ascribe hypertrophic cardiomyopathies to respiratory chain enzyme abnormalities in all three cases (complex I, two cases; multiple enzyme deficiency, one case). The respiratory chain enzyme activity ratios, which are normally constant irrespective of the tissue tested, were markedly abnormal in all three patients (cytochrome c oxidase/reduced nicotinamide-adenine dinucleotide cytochrome c reductase, 4.6 to 10.4; normal mean +/- 1 SD, 2.9 +/- 0.5). We conclude that mitochondrial disorders should be regarded as potential causes of hypertrophic cardiomyopathy in early infancy. Because cardiac catheterization is routinely performed for hemodynamic investigation of cardiomyopathies, we suggest that endomyocardial biopsies be considered as a tool for early detection of mitochondrial cardiomyopathies, especially in hypertrophic forms of the disease.
一方面考虑到不明原因的肥厚型心肌病比例较高，另一方面考虑到几种线粒体疾病中会出现心肌病，我们推测婴儿期孤立性肥厚型心肌病偶尔可能是氧化磷酸化缺陷的结果。通过一种缩小规模的技术，我们能够对3例同心性肥厚型心肌病患者（直径缩短率为18%至27%；正常均值±1标准差为33±3%）以及对照受试者的微量心内膜组织（1毫克）进行氧化磷酸化研究。尽管患者心内膜活检标本中的呼吸链酶绝对活性处于正常低限范围内，但通过测定活性比值，我们在所有3例病例中均将肥厚型心肌病归因于呼吸链酶异常（复合体I，2例；多种酶缺乏，1例）。呼吸链酶活性比值通常与所检测的组织无关而保持恒定，但在所有3例患者中均明显异常（细胞色素c氧化酶/还原型烟酰胺腺嘌呤二核苷酸细胞色素c还原酶，4.6至10.4；正常均值±1标准差，2.9±0.5）。我们得出结论，线粒体疾病应被视为婴儿早期肥厚型心肌病潜在病因。由于对心肌病进行血流动力学研究时常规进行心导管检查，我们建议将心内膜活检视为早期检测线粒体心肌病尤其是肥厚型疾病的一种手段。
