Willemsen Marjolein, Rodenburg Richard J T, Teszas Alexandra, van den Heuvel Lambert, Kosztolanyi Gyorgy, Morava Eva
Department of Pediatrics, Nijmegen Centre for Mitochondrial Disorders, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 Nijmegen, HB, The Netherlands.
Mitochondrion. 2006 Jun;6(3):155-9. doi: 10.1016/j.mito.2006.03.001. Epub 2006 May 19.
Biochemical analysis was performed in muscle tissue and in fibroblasts of four unrelated females consecutively diagnosed with a 'de novo' point mutation in the PDHA1 gene. Pyruvate dehydrogenase E1 subunit deficiency was confirmed in the muscle sample of all patients, however, in three out of four cases the activity of the pyruvate dehydrogenase complex in fibroblasts showed a normal activity. A skewed inactivation was confirmed of the maternal X chromosome in fibroblasts in all children. Due to the possibility of a skewed X inactivation pattern enzyme measurements in fibroblasts are not always reliable for the diagnosis of a PDHc defect in females. Based on the overlapping features of PDHc deficiency with those of the disorders of the oxidative phosphorylation we suggest performing a fresh muscle biopsy for detailed biochemical analysis in females with a suspected pyruvate dehydrogenase deficiency, followed by molecular genetic analysis of the PDHA1 gene.
对连续诊断出在PDHA1基因中存在“新发”点突变的四名无血缘关系女性的肌肉组织和成纤维细胞进行了生化分析。所有患者的肌肉样本均证实存在丙酮酸脱氢酶E1亚基缺乏症，然而，在四分之三的病例中，成纤维细胞中丙酮酸脱氢酶复合物的活性显示正常。所有患儿的成纤维细胞中均证实母源X染色体存在偏态失活。由于存在X失活模式偏态的可能性，因此成纤维细胞中的酶测量对于女性PDHc缺陷的诊断并不总是可靠的。基于PDHc缺乏症与氧化磷酸化疾病的重叠特征，我们建议对疑似丙酮酸脱氢酶缺乏症的女性进行新鲜肌肉活检以进行详细的生化分析，随后对PDHA1基因进行分子遗传学分析。
