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

众所周知，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缺陷引起的。因此，有必要对这些酶的活性进行检测以进行诊断。这些系统的诊断通常是通过皮肤成纤维细胞进行的。在本研究中，通过检测丙酮酸脱氢酶复合体(PDHC)的活性来研究丙酮酸代谢的各种酶。正常对照的人淋巴母细胞经EB病毒转化后，其丙酮酸羧基酶(PC)、磷酸烯醇丙酮酸羧基酶(PC)和呼吸链酶(RBC)的活性均在正常范围内。对于用成纤维细胞诊断PDHC或PC缺陷的患者，也可以用培养的淋巴母细胞进行诊断。此外，通过肌肉活检诊断呼吸链功能障碍的患者可以通过培养的淋巴母细胞进行诊断。因此，培养的淋巴母细胞在研究丙酮酸代谢功能障碍方面是有用的。此外，与皮肤成纤维细胞相比，培养的淋巴母细胞更容易建立。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.