Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Kuroda Y
Department of Paediatrics, School of Medicine, University of Tokushima, Japan.
Eur J Pediatr. 1998 Aug;157(8):648-52. doi: 10.1007/s004310050903.
Lactic acidaemia is sometimes associated with a defect of the pyruvate dehydrogenase complex (PDHC), catalysing the thiamine-dependent decarboxylation of pyruvate. The activity of PDHC for different thiamine pyrophosphate (TPP) concentrations was determined in 13 patients with lactic acidaemia, clinically responsive to thiamine treatment in order to assess the role of PDHC in the aetiology of thiamine-responsive lactic acidaemia. Culture of lymphoblastoid cells and skin fibroblasts and muscle biopsies were performed in these 13 patients. The activity of PDHC to sodium dichloroacetate (DCA), known as the activator of PDHC, was also examined. Three groups were identified according to PDHC activity. Group 1 (two patients) displayed very low PDHC activity, which was not increased by DCA. This PDHC activity increased at high TPP concentrations. Group 2 (five patients) displayed below normal PDHC activity at low TPP concentrations, increased by DCA. This PDHC activity became normal at high TPP concentrations. PDHC deficiency in these patients of groups 1 and 2 was due to a decreased affinity of PDHC for TPP. Group 3 included six patients with normal PDHC activity at low as well as high TPP concentrations. This PDHC activity was increased by DCA.
High concentrations of TPP may be required for maximal activity of PDHC in some patients with lactic acidaemia. The assay of PDHC activity, performed at a low concentration of TPP (1 x 10(-4)mM) allows selection of patients with thiamine-responsive lactic acidaemia.
乳酸血症有时与丙酮酸脱氢酶复合体（PDHC）缺陷有关，该复合体催化硫胺素依赖的丙酮酸脱羧反应。对13例乳酸血症患者测定了不同硫胺素焦磷酸（TPP）浓度下PDHC的活性，这些患者对硫胺素治疗有临床反应，以评估PDHC在硫胺素反应性乳酸血症病因中的作用。对这13例患者进行了淋巴母细胞和皮肤成纤维细胞培养以及肌肉活检。还检测了PDHC对已知的PDHC激活剂二氯乙酸钠（DCA）的活性。根据PDHC活性分为三组。第1组（2例患者）PDHC活性极低，DCA不能使其增加。该PDHC活性在高TPP浓度时增加。第2组（5例患者）在低TPP浓度时PDHC活性低于正常，DCA可使其增加。该PDHC活性在高TPP浓度时恢复正常。第1组和第2组这些患者的PDHC缺乏是由于PDHC对TPP的亲和力降低。第3组包括6例患者，其在低和高TPP浓度时PDHC活性均正常。该PDHC活性可被DCA增加。
对于一些乳酸血症患者，可能需要高浓度的TPP才能使PDHC发挥最大活性。在低浓度TPP（1×10⁻⁴mM）下进行的PDHC活性测定可筛选出硫胺素反应性乳酸血症患者。
