Eirís J, Alvarez-Moreno A, Briones P, Alonso-Alonso C, Castro-Gago M
Departamento de Pediatría, Hospital General de Galicia, Clínico Universitario, Santiago de Compostela, España.
Rev Neurol. 1996 Oct;24(134):1272-5.
Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and severe global developmental delay. A deficiency of PDH E1 alpha, a subunit of the PDH complex is a prominent cause of congenital lactic acidosis. The E1 alpha cDNA and corresponding genomic DNA have been located in the short arm of the X-chromosome (Xp22-1). A isolated 'cerebral' lactic acidosis with cerebral dysgenesis is a recognized pattern of presentation of PDH deficiency. Here, we report clinical features, magnetic resonance, and biochemical studies of two females aged 6 months (case 1) and 26 months (case 2). Both had severe development delay, minor dysmorphic features, microcephaly, severe hypoplasia of the corpus callosum, cerebral atrophy, ventricular dilatation and increase in serum lactate levels without systemic acidosis. Urinary organic acid profile was compatible with PDH deficiency. Increased CSF lactate and pyruvate levels and reduced total PDH and PDH E1 activities in muscle and fibroblasts were observed in case 1. Otherwise, decreased total PDH activity in muscle but not in fibroblasts was seen in case 2. The PDH E1á gene was sequenced in the case 1 and a deletion in exon 7 was demonstrated. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.
丙酮酸脱氢酶（PDH）缺乏是原发性乳酸性酸中毒和严重全球发育迟缓的主要原因。PDH复合物的一个亚基PDH E1α缺乏是先天性乳酸性酸中毒的一个突出原因。E1α cDNA和相应的基因组DNA已定位在X染色体的短臂（Xp22 - 1）上。一种伴有脑发育异常的孤立性“脑性”乳酸性酸中毒是PDH缺乏的一种公认表现形式。在此，我们报告了两名女性患者的临床特征、磁共振成像和生化研究结果，这两名患者年龄分别为6个月（病例1）和26个月（病例2）。两人均有严重发育迟缓、轻微畸形特征、小头畸形、胼胝体严重发育不全、脑萎缩、脑室扩张以及血清乳酸水平升高但无全身酸中毒。尿有机酸谱与PDH缺乏相符。在病例1中观察到脑脊液乳酸和丙酮酸水平升高，肌肉和成纤维细胞中总PDH和PDH E1活性降低。否则，在病例2中可见肌肉中总PDH活性降低，但成纤维细胞中未降低。对病例1的PDH E1α基因进行了测序，结果显示外显子7存在缺失。女性患者出现畸形并伴有严重脑畸形时，值得进行代谢评估，包括测定脑脊液中的乳酸和丙酮酸水平。
