Haworth J C, Perry T L, Blass J P, Hansen S, Urquhart N
Pediatrics. 1976 Oct;58(4):564-72.
A Canadian Indian family is described in which three of the children were mentally retarded, and had seizures and other neurological abnormalities. They had chronic metabolic acidosis associated with elevated blood levels of lactate, pyruvate, and alanine. Two of the children excreted large amounts of pyruvic and alpha-ketoglutaric acids in the urine and had elevated plasma levels of glutamic acid and proline. Hypoglycemia occurred with fasting in two of the children. Treatment with pharmacological doses of thiamine, lipoic acid, biotin, riboflavin, and various dietary regimes was without effect. One child died at 3 1/2 months and another at 4 1/2 months; the third is still alive at 23 months of age. Enzyme assays revealed a low level of activity of both the pyruvate and alpha-ketoglutarate dehydrogenase complexes in cultured fibroblasts of one of the sibs. These patients appeared to have partial defects in the oxidation of pyruvate, as well as of alpha-ketoglutarate within the tricarboxylic acid cycle.
本文描述了一个加拿大印第安家庭，该家庭中有三个孩子智力发育迟缓，伴有癫痫发作和其他神经学异常。他们患有慢性代谢性酸中毒，同时血液中乳酸、丙酮酸和丙氨酸水平升高。其中两个孩子尿液中排出大量丙酮酸和α-酮戊二酸，血浆中谷氨酸和脯氨酸水平升高。两个孩子空腹时出现低血糖。给予药理剂量的硫胺素、硫辛酸、生物素、核黄素以及各种饮食方案治疗均无效。一个孩子在3个半月时死亡，另一个在4个半月时死亡；第三个孩子在23个月时仍然存活。酶分析显示其中一个同胞培养的成纤维细胞中丙酮酸脱氢酶复合体和α-酮戊二酸脱氢酶复合体的活性水平较低。这些患者似乎在丙酮酸氧化以及三羧酸循环中α-酮戊二酸氧化方面存在部分缺陷。
