The cause of autism may be faulty mitochondria 线粒体缺陷可能是患自闭症的原因
Dec 1st 2010
AUTISM is a puzzling phenomenon. In its pure form it is an inability to understand the emotional responses of others that is seen in people of otherwise normal―sometimes above normal―intelligence. However, it is often associated with other problems, and can also appear in mild and severe forms. This variability has led many people to think of it as a spectrum of symptoms rather than a single, clear-cut syndrome. And that variability makes it hard to work out what causes it.
自闭症是奇怪的现象。纯粹的孤独症表现为不能理解正常人情感反应。 然而，自闭症常常伴随其它或轻微或严重的问题。该病的多变令许多人不把它的症状看成单一的而是一系列症状，其多变也使人们难以找出病因。
There is evidence of genetic influence, but no clear pattern of inheritance. The thought that the underlying cause may be hereditary, though, is one reason for disbelieving the hypothesis, which gained traction a few years ago but is now discredited, that measles vaccinations cause autism.
有一些证据表明患病受基因影响，但没有明显的遗传路径。然而，遗传因素导致自闭症的想法，却是人们不信麻疹疫苗导致自闭症这个假说的原因之一，这个假说几年前有很多人相信、如今为人们怀疑。
One suggestion that does pop up from time to time is that the process which leads to autism involves faulty mitochondria. The mitochondria are a cell's powerpacks. They disassemble sugar molecules and turn the energy thus liberated into a form that biochemical machinery can use. Mitochondrial faults could be caused by broken genes, by environmental effects, or by a combination of the two.
时不时有人提出导致自闭症的过程与有缺陷的线粒体有关。线粒体是细胞的能量库，它们分解糖分子，把能量转化成生化反应能够利用的形式。导致线粒体缺陷的因素可能有，受损基因、环境影响、或是两者皆有。
Nerve cells have a huge demand for energy, so a failure of the mitochondria would certainly affect them. The question is, could it cause autism? To try to find out Cecilia Giulivi of the University of California, Davis, and her colleagues studied the mitochondria of ten children, aged between two and five years, who had been diagnosed with autism. They have just published their results in the Journal of the American Medical Association.
神经细胞对能量需求巨大，因此线粒体的失灵必然影响它们。问题是，这能导致自闭症么？为了找出答案，加州大学达维斯分校的Cecilia Giulivi及其同事研究了十名两岁到五岁被诊断为自闭症的儿童的线粒体。他们刚刚在美国医学协会杂志上发表了研究成果。
Extracting nerve cells from the brains of children for a study like this is obviously out of the question. Instead, Dr Giulivi used immune-system cells called lymphocytes as surrogates. Lymphocytes, like nerve cells, use a lot of energy and thus rely heavily on their mitochondria. They are also easy to extract from blood. Dr Giulivi and her colleagues did just that, and then examined the activity of the lymphocytes' mitochondria.
把神经细胞从儿童脑中抽取出来显然不可能。Giulivi博士用免疫系统中的淋巴细胞作为替代。淋巴细胞和神经细胞一样需要很多能量，因此很大程度依赖于线粒体。它们容易从血液中采集。Giulivi博士他们就是这样做的，然后研究淋巴细胞中线粒体的活动。
The children in question were randomly selected from a previous study on autism. They were matched with ten children of similar ages and ethnic backgrounds who were developing normally. Dr Giulivi found that mitochondria from children with autism consumed far less oxygen than those from the control group. That is a sign of lower activity. One important set of enzymes―NADH oxidases―used, on average, only a third as much oxygen in autistic children as they did in non-autists, and eight of the autistic children had significantly lower NADH-oxidase activity than is normal.
研究的儿童是从之前自闭症研究中随机选出的。他们与十个年龄、种族背景相仿健康孩子配对比较。Giulivi博士发现自闭症儿童组线粒体消耗的氧比控制组少许多。这是不活跃的表现。 一组重要的酶――还原型辅酶氧化酶，在自闭症儿童中平均使用的氧仅为在正常儿童中的三分之一，8个孤独症儿童的线粒体中的的还原性辅酶氧化活动远不及在正常儿童中的活跃。
The mitochondria of the autistic children also leaked damaging oxygen-rich chemicals such as hydrogen peroxide. These are a normal by-product of mitochondrial activity, but are usually mopped up by special enzymes before they can escape and cause harm―for instance, by damaging a cell's DNA. The level of hydrogen peroxide in the cells of autistic children was twice that found in non-autists. Such high levels suggest the brains of autistic children are exposed to a lot of oxidative stress, something that would probably cause cumulative damage.
自闭症儿童的线粒体释放有害的富氧化学物，比如过氧化氢。这是线粒体活动中的副产品，但在他们游离变得有害之前，比如，破坏细胞的脱氧核糖核酸（DNA），会由特殊的酶清除干净。 在自闭症儿童细胞中的过氧化氢是正常儿童的两倍。这样的高浓度预示了自闭症儿童的大脑处于氧化压力中，这很有可能日积月累形成破坏。
These results need to be taken with caution. First, ten is an extremely small sample. Second, on the face of things, mitochondrial diseases appear far rarer than autism. They are diagnosed in fewer than six per 100,000 people in America, while autism of some sort is seen in as many as one in 110. Moreover, previous attempts to show a link have come up with a much weaker correlation between the two phenomena. A study of 69 autistic children that was published in 2005 found mitochondrial abnormalities in only five of them. That is higher than the background rate of mitochondrial disease, but nevertheless suggests that faulty mitochondria are not the only cause of autistic symptoms. This study did, however, use a broader sample of the autistic spectrum than Dr Giulivi's, and looked at muscle cells, whose metabolic profiles are very different from nerve cells and lymphocytes.
我们应该谨慎看待研究结果应该。第一，调查样本为十个，规模很小。第二，显然，线粒体疾病比自闭症罕见得多。在美国诊断患有线粒体疾病的人低于十万分之六，而患孤独症的为110分之一。 另外，之前试图找出两者的联系，却发现两者之间更微弱的关联。2005年公布的对69名自闭症儿童的研究发现只有五名儿童的线粒体有异常。这比普遍的高，但也说明有缺陷的线粒体不是唯一的导致自闭症症状的原因。然而该研究使用了比Giulivi博士范围更大的自闭症症状做研究，并且研究了肌肉细胞，其新陈代谢与神经细胞和淋巴细胞的过程大相径庭。
It is also important to remember, in studies like this, that correlation is not causation. Some third effect could be triggering both the symptoms of autism and the mitochondrial dysfunction. If it is really the mitochondria that are causing the problem, though, there is another hypothesis that needs to be addressed. This is that external triggers might expose such mitochondrial weaknesses earlier than would otherwise be the case.
需要认识到重要一点是，像这样的研究中，关联性不等于因果关系。可能是某种第三方因素既引发了自闭症又导致了线粒体缺陷。若果真是线粒体引起的毛病，那么我们需要能够解释另外一个假设：外来的诱发因素可能把这样的线粒体缺陷提早暴露出来。
In 2008 an American court awarded damages to a child after she developed health problems following routine childhood vaccinations. America's Department of Health and Human Services looked into the child's medical history and concluded that vaccines had significantly aggravated an underlying inherited mitochondrial disorder that predisposed her to metabolic problems that caused brain damage with features of autism.
2008年美国一个法庭判定赔偿一名儿童接受照常的儿童疫苗后而得病的造成的损失。美国卫生部检查了儿童的病历，认定疫苗大大加剧了这名儿童遗传的线粒体紊乱，这种紊乱容易导致新陈代谢问题，进一步导致有自闭症症状的脑部损伤。
The genetic condition in this particular case is rare: only four other examples are known. And no scientist―least of all Dr Giulivi―is suggesting that the new study bears on the question of environmental triggers of mitochondrial malfunction. But if faulty mitochondria do turn out to be a cause of autism, even if not in all cases, that question will have to be investigated. And you can bet your bottom dollar that somewhere out there is a lawyer wondering whether he can do just that.
该案例中的基因状况很罕见，除此之外已知的仅有四例。没有科学家，尤其是Giulivi博士认为新研究牵涉了是否环境因素会诱发线粒体缺陷这个问题。但如果缺陷线粒体的确是自闭症的成因之一（若不是所有的情况都是这样），这个问题就得深入研究了。可以打保票的是，肯定有律师在琢磨他能在这件事上做出点儿什么文章
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