DEFICIENCY OF DIHYDROLIPOYL DEHYDROGENASE (A COMPONENT OF PYRUVATE AND ALPHA-KETOGLUTARATE DEHYDROGENASE COMPLEXES) - CAUSE OF CONGENITAL CHRONIC LACTIC-ACIDOSIS IN INFANCY
DEFICIENCY OF DIHYDROLIPOYL DEHYDROGENASE (A COMPONENT OF PYRUVATE AND ALPHA-KETOGLUTARATE DEHYDROGENASE COMPLEXES) - CAUSE OF CONGENITAL CHRONIC LACTIC-ACIDOSIS IN INFANCY
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DOI：
10.1203/00006450-197712000-00006
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发表时间：
1977-01-01
影响因子：
3.6
通讯作者：
SHERWOOD, WG
中科院分区：
文献类型：
--
作者：
ROBINSON, BH;TAYLOR, J;SHERWOOD, WG
一名男婴在 7 个月大时死亡。随着年龄的增长，进行性神经功能恶化和持续性代谢性酸中毒。生前调查显示，该孩子的血液丙酮酸、乳酸和α-酮戊二酸升高，支链氨基酸升高，偶尔出现低血糖。使用硫胺素-HCl（2 g/kg 每 24 小时）或硫胺素四氢糠基二硫化物的辅因子治疗对患者的临床或生化状态没有可测量的影响。尸检显示，所有测试组织（肝、脑、肾、骨骼肌和心脏）中关键糖异生酶水平正常，但丙酮酸脱氢酶活性缺乏。对丙酮酸脱氢酶复合物的个体活性的检查显示丙酮酸脱羧酶 [EC 4.1.1.1] (E1) 在肝脏和其他组织中正常。所有测试的组织中都缺乏二氢硫辛酰脱氢酶[EC 1.6.4.3] (E3)。 α-酮戊二酸脱氢酶复合物的总活性依赖于E3，在所有测试的组织中均缺乏。这种酶的缺乏与患者的临床和生化状态有关。
A male child died at 7 mo. of age with progressive neurologic deterioration and persistent metabolic acidosis. Investigations during life showed this child to have elevated blood pyruvate, lactate and .alpha.-ketoglutarate as well as elevation of branched chain amino acids and occasional hypoglycemia. Cofactor therapy using thiamine-HCl (2 g/kg per 24 h) or thiamine tetrahydrofurfuryl disulfide had no measurable effect on the clinical or biochemical status of the patient. Tissue taken postmortem showed normal levels of key gluconeogenic enzymes but a deficiency in activity of pyruvate dehydrogenase in all tissues tested (liver, brain, kidney, skeletal muscle and heart). Examination of individual activities of the pyruvate dehydrogenase complex showed pyruvate decarboxylase [EC 4.1.1.1] (E1) to be normal in liver and other tissues. Dihydrolipoyl dehydrogenase [EC 1.6.4.3] (E3) was deficient in all tissues tested. .alpha.-Ketoglutarate dehydrogenase complex, which depends on E3 for its total activity, was deficient in all tissues tested. The absence of this enzyme is discussed in relation to the clinical and biochemical status of the patient.