MATERNAL HYPERHOMOCYSTEINEMIA - A RISK FACTOR FOR NEURAL-TUBE DEFECTS
MATERNAL HYPERHOMOCYSTEINEMIA - A RISK FACTOR FOR NEURAL-TUBE DEFECTS
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DOI：
10.1016/0026-0495(94)90004-3
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发表时间：
1994-12-01
影响因子：
9.8
通讯作者：
ESKES, TKAB
中科院分区：
文献类型：
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作者：
STEEGERSTHEUNISSEN, RPM;BOERS, GHJ;ESKES, TKAB
母亲的维生素状况，特别是叶酸，参与神经管缺陷（NTDs）的发病机制。母亲服用叶酸可以预防这些畸形。叶酸有益作用的确切代谢机制尚不清楚。在这项研究中，我们专注于同型半胱氨酸的积累，这可能是由于叶酸，维生素B-12和维生素B-6的代谢异常。我们研究了未怀孕的妇女，其中41人生下了NTD婴儿，50名对照妇女以前有正常的后代。测定包括空腹状态和摄入甲硫氨酸负荷后6小时的血浆总同型半胱氨酸。此外，我们还测量了空腹血液中叶酸、维生素B-12和维生素B的水平（6）。在有NTD婴儿的妇女组中，基础同型半胱氨酸和蛋氨酸负荷后同型半胱氨酸的平均值显著增加。在这些受试者和两个对照组中，蛋氨酸摄入后的值超过平均对照超过2个标准差。来自这些甲硫氨酸不耐受妇女的皮肤成纤维细胞中的胱硫醚合酶水平在正常范围内。我们的研究结果表明，由于获得性（即营养性）或遗传性叶酸或维生素B-12代谢紊乱，导致同型半胱氨酸再甲基化为甲硫氨酸的障碍。增加的同型半胱氨酸水平可以通过服用维生素B或叶酸来恢复正常。因此，我们认为围孕期给予叶酸预防NTDs可以有效纠正轻中度高同型半胱氨酸血症。
The maternal vitamin status, especially of folate, is involved in the pathogenesis of neural-tube defects (NTDs). Maternal folate administration can prevent these malformations. The precise metabolic mechanism of the beneficial effect of folate is unclear. In this study we focus on homocysteine accumulation, which may derive from abnormalities of metabolism of folate, vitamin B-12, and vitamin B-6. We studied nonpregnant women, 41 of whom had given birth to infants with NTDs and 50 control women who previously had normal offspring. The determinations included the plasma total homocysteine both in the fasting state and 6 hours after the ingestion of a methionine load. In addition, we measured the fasting blood levels of folate, vitamin B-12, and vitamin b(6). The mean values for both basal homocysteine and homocysteine following a methionine load were significantly increased in the group of women who previously had infants with NTDs. In nine of these subjects and two controls, the values after methionine ingestion exceeded the mean control by more than 2 standard deviations. Cystathionine synthase levels in skin fibroblasts derived from these methionine-intolerant women were within the normal range. Our findings suggest a disorder in the remethylation of homocysteine to methionine due to an acquired (ie, nutritional) or inherited derangement of folate or vitamin B-12 metabolism. Increased homocysteine levels can be normalized by administration of vitamin Bs or folate. Therefore, we suggest that the prevention of NTDs by periconceptional folate administration may effectively correct a mild to moderate hyperhomocysteinemia.