Brattström L, Israelsson B, Norrving B, Bergqvist D, Thörne J, Hultberg B, Hamfelt A
Department of Neurology, University Hospital, University of Lund, Sweden.
Atherosclerosis. 1990 Feb;81(1):51-60. doi: 10.1016/0021-9150(90)90058-q.
Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.
由于5-磷酸吡哆醛（PLP）依赖性胱硫醚β-合酶（CBS）的遗传缺陷或维生素B12和叶酸代谢中的酶缺陷导致的严重高同型半胱氨酸血症与极早发的血管疾病相关。因此，我们研究了72例55岁前出现脑、颈动脉或主-髂血管闭塞性动脉疾病患者的同型半胱氨酸代谢情况。20例患者（28%）存在基础高同型半胱氨酸血症；26例患者（36%）口服蛋氨酸负荷后血浆同型半胱氨酸异常升高，超过46例对照的最高值，且在20例因CBS缺乏导致的同型胱氨酸尿症杂合子范围内。基础血浆同型半胱氨酸含量与维生素B12和叶酸浓度呈强烈负相关。大多数患者血浆PLP降低，但PLP与同型半胱氨酸值之间无相关性。20例患者接受盐酸吡哆醇（240mg/天）和叶酸（10mg/天）治疗4周后，空腹同型半胱氨酸平均降低53%，蛋氨酸反应平均降低39%。这些数据表明，相当一部分早发血管疾病患者存在同型半胱氨酸代谢受损，这可能导致血管疾病，且受损的代谢可以轻松改善且无副作用。
