Li S C, Stewart P M
Institute of Clinical Pathology and Medical Research, Westmead Hospital, Sydney, Australia.
Pathology. 1999 Aug;31(3):221-4. doi: 10.1080/003130299105025.
Deficiency of cystathionine beta-synthase (CBS) is the commonest cause of primary homocystinuria. Homocysteine metabolism is intimately linked with the metabolism of folate, vitamin B12 (cobalamin) and pyridoxine. It is hypothesised that the pathogenesis of neuropsychiatric manifestations in homocystinuria, folate and cobalamin deficiencies are related to imbalance neurotransmitters in the CNS through disturbances in the pathways linking the metabolism of homocysteine and these vitamins. Although neuropsychiatric disorders are relatively common among patients with homocystinuria, it is not well recognised as the causative factor among patients presenting with neuropsychiatric disorders. A 31 year old woman presented with a three week history of delirium and inappropriate and labile affect. There was no history suggestive of drug or alcohol abuse, nutritional deficiency or organic disorders. EEG, cerebral CT, MRI and microbiological investigations did not reveal any organic causes. Because of a diagnosis of pyridoxine-responsive homocystinuria seven years previously, the possibility of homocystinuria was considered and investigated. Laboratory tests revealed macrocytosis and a high concentration of urinary total homocystine. Commencement of pyridoxine at 400 mg/day resulted in disappearance of homocystine in urine within four days with remarkable clinical improvement. Homocystinuria should be considered in the differential diagnosis of unexplained neuropsychiatric disorders in patients who have past or family history of homocystinuria, mental retardation, thromboembolic episodes, vascular diseases or clinical and laboratory features resembling folate and/or vitamin B12 deficiencies. Homocystinuria-associated neuropsychiatric disturbances can easily be treated with pyridoxine in 50% of cases.
胱硫醚β-合酶（CBS）缺乏是原发性高胱氨酸尿症最常见的病因。同型半胱氨酸代谢与叶酸、维生素B12（钴胺素）和吡哆醇的代谢密切相关。据推测，高胱氨酸尿症、叶酸和钴胺素缺乏时神经精神症状的发病机制与中枢神经系统中神经递质失衡有关，这种失衡是通过同型半胱氨酸与这些维生素代谢之间的途径紊乱导致的。虽然神经精神障碍在高胱氨酸尿症患者中相对常见，但在出现神经精神障碍的患者中，它并未被充分认识为致病因素。一名31岁女性出现谵妄、情感不恰当且不稳定，病程3周。无药物或酒精滥用、营养缺乏或器质性疾病史。脑电图、脑部CT、MRI及微生物学检查未发现任何器质性病因。由于7年前诊断为吡哆醇反应性高胱氨酸尿症，故考虑并调查了高胱氨酸尿症的可能性。实验室检查显示大细胞性贫血及尿总同型半胱氨酸浓度升高。开始每日服用400mg吡哆醇后，4天内尿中同型半胱氨酸消失，临床症状明显改善。对于有高胱氨酸尿症、智力发育迟缓、血栓栓塞事件、血管疾病病史或家族史，或有类似叶酸和/或维生素B12缺乏的临床及实验室特征的患者，在不明原因神经精神障碍的鉴别诊断中应考虑高胱氨酸尿症。50%的高胱氨酸尿症相关神经精神障碍患者用吡哆醇治疗很容易治愈。
