Magner M, Vinšová K, Tesařová M, Hájková Z, Hansíková H, Wenchich L, Ješina P, Smolka V, Adam T, Vaněčková M, Zeman J, Honzík T
Department of Pediatrics and Adolescent Medicine, Charles University, Prague, Czech Republic.
Prague Med Rep. 2011;112(1):18-28.
The most common cause of pyruvate dehydrogenase complex (PDHc) deficiency is the deficit of the E1α-subunit. The aim of this study was to describe distinct course of the disease in two boys with mutations in PDHA1 gene and illustrate the possible obstacles in measurement of PDHc activity. Clinical data and metabolic profiles were collected and evaluated. PDHc and E1α-subunit activities were measured using radiometric assay. Subunits of PDHc were detected by Western blot. PDHA1 gene was analysed by direct sequencing. In patient 1, the initial hypotonia with psychomotor retardation was observed since early infancy. The child gradually showed symptoms of spasticity and arrest of psychomotor development. In patient 2, the disease manifested by seizures and hyporeflexia in the toddler age. The diagnosis was confirmed at the age of seven years after attacks of dystonia and clinical manifestation of myopathy with normal mental development. Brain MRI of both patients revealed lesions typical of Leigh syndrome. Enzymatic analyses revealed PDHc deficiency in isolated lymphocytes in the first but not in the second patient. The direct measurement of PDH E1-subunit revealed deficiency in this individual. In patient 1, a novel hemizigous mutation c.857C>T (Pro250Leu) was detected in the X-linked PDHA1 gene. Mutation c.367C>T (Arg88Cys) was found in patient 2. We present first two patients with PDHc deficit due to mutations in PDHA1 gene in the Czech Republic. We document the broad variability of clinical symptoms of this disease. We proved that normal PDHc activity may not exclude the disease.
丙酮酸脱氢酶复合体（PDHc）缺乏症最常见的病因是E1α亚基的缺陷。本研究的目的是描述两名携带PDHA1基因突变的男孩所患疾病的不同病程，并说明测量PDHc活性时可能遇到的障碍。收集并评估了临床数据和代谢谱。使用放射性测定法测量PDHc和E1α亚基的活性。通过蛋白质印迹法检测PDHc的亚基。通过直接测序分析PDHA1基因。在患者1中，自婴儿早期就观察到最初的肌张力减退伴精神运动发育迟缓。该患儿逐渐出现痉挛症状并精神运动发育停滞。在患者2中，疾病在幼儿期表现为癫痫发作和反射减退。在出现肌张力障碍发作以及精神发育正常但有肌病临床表现后，该患者在7岁时确诊。两名患者的脑部磁共振成像（MRI）均显示出典型的 Leigh 综合征病变。酶学分析显示，第一名患者的分离淋巴细胞中存在PDHc缺乏症，而第二名患者则没有。对PDH E1亚基的直接测量显示该个体存在缺陷。在患者1中，在X连锁的PDHA1基因中检测到一个新的半合子突变c.857C>T（Pro250Leu）。在患者2中发现了c.367C>T（Arg88Cys）突变。我们报告了捷克共和国首例因PDHA1基因突变导致PDHc缺乏的两名患者。我们记录了这种疾病临床症状的广泛变异性。我们证明正常的PDHc活性并不能排除该病。
