The Clinical and Biochemical Spectrum of Human Pyruvate Dehydrogenase Complex Deficiency
The Clinical and Biochemical Spectrum of Human Pyruvate Dehydrogenase Complex Deficiency
复制标题
人丙酮酸脱氢酶复合物缺乏症的临床和生化谱
DOI：
10.1111/j.1749-6632.1989.tb15011.x
复制
发表时间：
1989
影响因子：
5.2
通讯作者：
H. Dahl
中科院分区：
文献类型：
--
作者：
G. Brown;R. M. Brown;R. Scholem;D. Kirby;H. Dahl
丙酮酸脱氢酶复合物（PDC）缺乏是婴幼儿原发性乳酸酸中毒的主要原因。在几乎所有的病例中，基本缺陷似乎是在PDC的El组分中，特别是在Ela亚基中。24尽管有许多关于人类PDC缺陷的报道，但关于这种疾病的发病率、临床和生化谱仍然存在重大争议。关于人类PDC缺乏症的一些混淆已经出现，因为通过测定来自患者的容易获得的样品中的酶复合物来建立诊断的困难。然而，更可靠的检测方法的发展，免疫化学方法的可用性，用于分析特定成分的结构变化，以及用于研究潜在遗传缺陷的重组DNA探针的分离，大大提高了诊断的准确性。PDC缺陷的异质性可以从最近报道的病例中评估，确信所描述的患者确实在PDC中具有原发性遗传缺陷。以下讨论将限于PDC的Ela组分中具有缺陷的患者。根据我们自己的经验和最近报道的病例，很明显，这种形式的PDC缺乏症在人类中是一种极其异质性的疾病。这种疾病的特征是代谢性酸中毒和神经功能障碍。与许多其他影响脑功能的先天性代谢缺陷相比，PDC缺乏症的特点是中枢神经系统（CNS）存在显著的结构异常。然而，在这种一般的临床表现中，症状的严重程度和病情的临床过程有很大的范围。在最严重的PDC缺乏症中，乳酸性酸中毒在出生后数小时内发生，血液乳酸浓度迅速达到高达10-20 mM的水平。4乳酸性酸中毒几乎总是对所有尝试的特异性治疗无效，大多数患者在新生儿期死亡。不太严重的PDC缺乏症患者一般出现较晚，其临床过程的特点是严重的乳酸酸中毒发作，往往是由并发疾病引起的。“血丙酮酸和
Pyruvate dehydrogenase complex (PDC) deficiency is a major cause of primary lactic acidosis in infants and young children.' In almost all cases, the basic defect appears to be in the El component of PDC and, in particular, in the Ela subunit.24 In spite of numerous reports of PDC deficiency in humans, there is still significant controversy concerning the incidence and the clinical and biochemical spectrum of this ~ondi t ion .~ Some of the confusion regarding PDC deficiency in humans has arisen because of difficulties in establishing the diagnosis by assay of the enzyme complex in readily available samples from patients. However, the development of more reliable assays,' the availability of immunochemical methods for analysis of structural changes in specific components of the and the isolation of recombinant DNA probes for studies of the underlying genetic defects8-" have greatly improved the accuracy of diagnosis. The heterogeneity of PDC deficiency can be assessed from recently reported cases with confidence that the patients described do indeed have a primary genetic defect in the PDC. The following discussion will be limited to patients with defects in the E l a component of PDC. From our own experience and from recently reported cases, it is apparent that this form of PDC deficiency in humans is an extremely heterogeneous condition. The characteristic features of the disorder are metabolic acidosis and neurological dysfunction. In contrast with many other inborn errors of metabolism which affect cerebral function, PDC deficiency is distinguished by the presence of significant structural abnormalities in the central nervous system (CNS). Within this general clinical presentation, however, there is a wide range in the severity of symptoms and the clinical course of the condition. In the most severe form of PDC deficiency, lactic acidosis develops within hours of birth and the blood lactate concentration rapidly attains levels as high as 10-20 mM.4 The lactic acidosis is almost always refractory to all attempts a t specific therapy, and most of these patients die in the newborn period. Patients with less severe forms of PDC deficiency generally present later, and their clinical course is characterized by episodes of severe lactic acidosis, often precipitated by intercurrent illness." Blood pyruvate and
丙酮酸脱氢酶复合物缺乏是亚急性坏死性脑病（Leigh 病）的原因。
影响因子：
8
作者：
Kretzschmar,HA;DeArmond,SJ;Koch,TK;Patel,MS;Newth,CJ;Schmidt,KA;Packman,S
通讯作者：
Packman,S