FUMARASE DEFICIENCY - A NEW CAUSE OF MITOCHONDRIAL ENCEPHALOMYOPATHY
FUMARASE DEFICIENCY - A NEW CAUSE OF MITOCHONDRIAL ENCEPHALOMYOPATHY
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DOI：
10.1056/nejm198608213150801
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发表时间：
1986-08-21
影响因子：
158.5
通讯作者：
HOPPEL, CL
中科院分区：
文献类型：
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作者：
ZINN, AB;KERR, DS;HOPPEL, CL
我们观察到一名患有线粒体脑肌病的男婴缺乏线粒体和胞浆形式的辅酶A酶，该男婴在一个月大时出现发育不良、发育迟缓、张力减退、大脑萎缩、乳酸和维生素C血症以及富马酸尿症。患者在8个月大时死亡。分离的骨骼肌线粒体在谷氨酸氧化中显示出选择性缺陷（每毫克线粒体蛋白每分钟消耗31 ng氧原子，而每毫克线粒体蛋白每分钟消耗94 ng氧原子）。19 [平均值±。5个对照组中的SD]）和琥珀酸盐（18对145 . ±.每毫克蛋白质每分钟18 ng氧原子），而分离的肝线粒体正常氧化这些和其他底物。在两个肝线粒体中几乎不存在富马酸酶活性（53对2878 . ±. 248 nmol/min/mg蛋白质[5个对照组]）和垂体-肌肉线粒体（23与1997 . ±. 717 nmol/min/mg [12个对照]）。 其他17种线粒体酶在肝脏和肌肉线粒体提取物中具有正常活性。在肝组织的匀浆中富马酸酶活性也显著降低（< 1对90 ± 0.01）。25 μ mol/分钟/克湿重[5个对照]）和骨骼肌（< 1对21 ± 0.5 μ mol/分钟/克湿重[5个对照]）。4 μ mol/分钟/克[5个对照]），表明线粒体和胞质中的脱氢酶都缺乏。富马酸盐线粒体内蓄积的器官差异可能是在骨骼肌线粒体中观察到的选择性氧化缺陷的原因，而不是肝脏线粒体。所有这些发现都与严重的复合酶缺乏症相一致。
We observed a deficiency of both the mitochondrial and cytosolic forms of fumarase in a male infant with mitochondrial encephalomyopathy who presented at one month of age with failure to thrive, developmental delay, hypotonia, cerebral atropy, lactic and pyruvic acidemia, and fumaric aciduria. The patient died at eight months of age. Isolated skeletal-muscle mitochondria showed selective defects in the oxidation of glutamate (31 ng atoms of oxygen consumed per minute per milligram of mitochondrial protein, as compared with 94 .+-. 19 [mean .+-. SD] in five controls) and of succinate (18 vs. 145 .+-. 18 ng atoms of oxygen per minute per milligram of protein), whereas isolated liver mitochondria oxidized these and other substrates normally. Fumarase activity was virtually absent in both liver mitochondria (53 vs. 2878 .+-. 248 nmol per minute per milligram of protein [5 controls]) and skeletal-muscle mitochondria (23 vs. 1997 .+-. 717 nmol per minute per milligram [12 controls]). Seventeen other mitochondrial enzymes had normal activity in both liver and muscle mitochondrial extracts. Fumarase activity was also significantly reduced in homogenates of liver tissue (< 1 vs. 90 .+-. 25 .mu.mol per minute per gram of wet weight [five controls]) and skeletal muscle (< 1 vs. 21 .+-. 4 .mu.mol per minute per gram [five controls]), indicating a deficiency of both mitochondrial and cytosolic fumarases. Organ differences in intramitochondrial accumulation of fumarate may have accounted for the selective oxidative defects observed in the skeletal-muscle mitochondria but not liver mitochondria. All these findings are consistent with a profound combined fumarase deficiency.