HOMOCYSTINURIA - A NEW INBORN ERROR OF METABOLISM ASSOCIATED WITH MENTAL DEFICIENCY
HOMOCYSTINURIA - A NEW INBORN ERROR OF METABOLISM ASSOCIATED WITH MENTAL DEFICIENCY
复制标题
DOI：
10.1136/adc.38.201.425
复制
发表时间：
1963-01-01
影响因子：
5.2
通讯作者：
CUSWORTH, DC
中科院分区：
文献类型：
--
作者：
CARSON, NAJ;DENT, CE;CUSWORTH, DC
对北方爱尔兰智力缺陷者尿液进行的一项生化调查显示，有2名具有相当特征性临床表现的兄弟姐妹不断分泌适量的氨基酸，与氰化物硝普钠试验中的胱氨酸反应相似。经色谱分析和经典化学方法鉴定，该异常氨基酸为L-同型胱氨酸。尿液排泄的机制是“溢出”机制。对母亲、2名患病同胞和正常同胞进行L-蛋氨酸负荷试验。结果最难解释。受影响的兄弟姐妹和母亲表现出代谢蛋氨酸的能力略有下降，尿蛋氨酸排泄量远大于预期，表明肾脏清除率较高。令人惊讶的是，高胱氨酸排泄在甲硫氨酸负荷后仅增加了一点。我们假设这里有一个先天的新陈代谢缺陷，详细的机制仍然不清楚。我们建议将该病命名为“同型胱氨酸尿症”。初步试验已经开始治疗额外的口服胱氨酸。我们的第一个假设是，该疾病的直接原因可能是由于代谢错误导致的胱氨酸缺乏症，该代谢错误阻止了甲硫氨酸向胱氨酸的正常转化，并且还表现为过量的密切相关的化合物同型胱氨酸的积累和排泄。然而，我们很难证实这一点。另一种假设是蛋氨酸转运系统的缺陷是主要原因。
Arising from a biochemical survey of urines from mental defectives in Northern Ireland it was revealed that 2 siblings with a rather characteristic clinical appearance constantly excrete moderate quantities of an amino acid reacting like cystine to the cyanide nitroprusside test. The abnormal amino acid was identified by chromatographic and classical chemical methods as L-homocystine. The mechanism of the urinary excretion is an "overflow" one. Loading tests with L-methionine were performed on the mother, the 2 affected siblings and on the normal sibling. The results were most difficult to interpret. The affected siblings and the mother show a slightly reduced ability to metabolize methionine, and a much larger than expected urinary methionine excretion, indicating high renal clearances. Homocystine excretion, surprisingly, only increased a little after the methionine load. We assume that there is an inborn error of metabolism here, the detailed mechanism remaining obscure. We suggest the name "homocystinuria" for the disease. Preliminary trials have begun of treatment by additional oral cystine. Our first hypothesis was that the immediate cause of the disease might be a cystine deficiency due to an error of metabolism that prevents the normal conversion of methionine into cystine and that also manifests itself by the accumulation and excretion of excessive quantities of the closely related compound homocystine. We are having difficulties, however, in confirming this. An alternative hypothesis is that a defect in methionine transport systems is the primary cause.