Enzymatic diagnosis of patients with congenital lactic acidemia on cultured lymphoblastoid cells

已知先天性乳酸血症是异质性的，是由丙酮酸代谢中多种酶活性的遗传决定缺陷引起的。因此，有必要测定这些酶的活性，以进行诊断。这些系统诊断通常通过使用皮肤成纤维细胞进行。本研究通过测定丙酮酸脱氢酶复合物（PDHC）的活性，研究了丙酮酸代谢的各种酶。在epstein - barrvirus转化的正常对照人淋巴母细胞中检测到丙酮酸羧化酶（PC）、磷酸烯醇丙酮酸羧化酶（phosphoenol pyruvate carboxykinase）和呼吸链酶（respiratory chain enzyme，呼吸链酶）的活性，得到了这些酶的正常范围。在用成纤维细胞诊断PDHC或PC缺乏的患者中，这些缺陷也可以用培养的淋巴母细胞样细胞诊断。此外，通过肌肉活检诊断的呼吸链功能障碍患者可以通过培养的淋巴母细胞样细胞进行诊断。因此，培养的淋巴母细胞样细胞可用于研究丙酮酸代谢功能障碍。此外，与皮肤成纤维细胞相比，培养的淋巴母细胞样细胞更容易建立。因此，淋巴母细胞系是系统诊断先天性乳酸血症的有用细胞。

Congenital lactic acidemia is known to be heterogenous and to be caused by genetically determined defects in the activities of a variety of enzymes in the pyruvate metabolism. Therefore, it is necessary to assay the activities of these enzymes for the diagnosis. These systematic diagnosis have been usually performed by using skin fibroblasts.In this study, the various enzymes of pyruvate metabolism were investigated by measuring the activities of pyruvate dehydrogenase complex (PDHC). pyruvate carboxylase (PC), phosphoenol pyruvate carboxykinase, and respiratory chain enzyme in Epstein-Barrvirus-transformed human lymphoblastoid cells from normal controls, resulting that we could get the normal range of the activities of these enzymes.In patients with deficiency of PDHC or PC diagnosed by using fibroblasts, these defects could be also diagnosed by using cultured lymphoblastoid cells. Furthermore, patients with dysfunction of respiratory chain diagnosed by biopsied muscle were able to be diagnosed by using cultured lymphoblastoid cells. Thus, cultured lymphoblastoid cells are useful in investigating the dysfunction of pyruvate metabolism. Furthermore, it is easy to establish cultured lymphoblastoid cells as compared with skin fibroblasts. Therefore, lymphoblastoid cells lines are useful cells for the systematic diagnosis of congenital lactic acidemia.