Zittoun J
Service d'Hématologie Biologique, Hôpital Henri Mondor, Creteil, France.
Baillieres Clin Haematol. 1995 Sep;8(3):603-16. doi: 10.1016/s0950-3536(05)80222-7.
Congenital errors of folate metabolism can be related either to defective transport of folate through various cells or to defective intracellular utilization of folate due to some enzyme deficiencies. Defective transport of folate across the intestine and the blood-brain barrier was reported in the condition 'Congenital Malabsorption of Folate'. This disease is characterized by a severe megaloblastic anaemia of early appearance associated with mental retardation. Anaemia is folate-responsive, but neurological symptoms are only poorly improved because of the inability to maintain adequate levels of folate in the CSF. A familial defect of cellular uptake was described in a family with a high frequency of aplastic anaemia or leukaemia. An isolated defect in folate transport into CSF was identified in a patient suffering from a cerebellar syndrome and pyramidal tract dysfunction. Among enzyme deficiencies, some are well documented, others still putative. Methylenetetrahydrofolate reductase deficiency is the most common. The main clinical findings are neurological signs (mental retardation, seizures, rarely schizophrenic syndromes) or vascular disease, without any haematological abnormality. Low levels of folate in serum, red blood cells and CSF associated with homocystinuria are constant. Methionine synthase deficiency is characterized by a megaloblastic anaemia occurring early in life that is more or less folate-responsive and associated with mental retardation. Glutamate formiminotransferase-cyclodeaminase deficiency is responsible for massive excretion of formiminoglutamic acid but megaloblastic anaemia is not constant. The clinical findings are a more or less severe mental or physical retardation. Dihydrofolate reductase deficiency was reported in three children presenting with a megaloblastic anaemia a few days or weeks after birth, which responded to folinic acid. The possible relationship between congenital disorders such as neural tube defects or dihydropteridine reductase deficiency and disturbances of folate metabolism are discussed. Neurological symptoms present in most of these congenital disorders highlight the role of folate in the central nervous system.
先天性叶酸代谢异常可能与叶酸通过各种细胞的转运缺陷有关，也可能与某些酶缺乏导致的叶酸细胞内利用缺陷有关。在“先天性叶酸吸收不良”的情况下，有报道称叶酸跨肠道和血脑屏障的转运存在缺陷。这种疾病的特征是早期出现严重的巨幼细胞贫血并伴有智力发育迟缓。贫血对叶酸有反应，但由于无法在脑脊液中维持足够的叶酸水平，神经症状仅得到轻微改善。在一个再生障碍性贫血或白血病高发的家族中，描述了一种细胞摄取的家族性缺陷。在一名患有小脑综合征和锥体束功能障碍的患者中，发现了叶酸转运至脑脊液的孤立缺陷。在酶缺乏症中，有些已有充分记录，有些仍属推测。亚甲基四氢叶酸还原酶缺乏是最常见的。主要临床发现是神经体征（智力发育迟缓、癫痫发作，很少有精神分裂症综合征）或血管疾病，无任何血液学异常。血清、红细胞和脑脊液中叶酸水平低并伴有高同型半胱氨酸尿症是持续存在的。甲硫氨酸合酶缺乏的特征是在生命早期出现巨幼细胞贫血，对叶酸或多或少有反应，并伴有智力发育迟缓。谷氨酸亚胺甲基转移酶-环脱氨酶缺乏导致亚胺甲基谷氨酸大量排泄，但巨幼细胞贫血并不持续存在。临床发现是或多或少严重的智力或身体发育迟缓。在三名出生后几天或几周出现巨幼细胞贫血的儿童中报告了二氢叶酸还原酶缺乏，这些贫血对亚叶酸有反应。讨论了神经管缺陷或二氢蝶啶还原酶缺乏等先天性疾病与叶酸代谢紊乱之间的可能关系。这些先天性疾病中大多数出现的神经症状突出了叶酸在中枢神经系统中的作用。
