Ramaekers V T, Blau N, Sequeira J M, Nassogne M-C, Quadros E V
Division of Child Neurology, University Hospital Liège, Belgium.
Neuropediatrics. 2007 Dec;38(6):276-81. doi: 10.1055/s-2008-1065354.
Reduced folate transport to the CNS was identified in two autism spectrum disorders, i.e., Rett syndrome and infantile low-functioning autism with neurological abnormalities. Twenty-five patients with early-onset low-functioning autism with or without neurological deficits, were evaluated for serum folate, cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5MTHF), and serum FR autoantibodies of the blocking type to determine the significance of folate receptor (FR) autoantibodies with respect to folate transport across the blood-CSF barrier. In spite of normal serum folate, CSF 5MTHF was low in 23 of 25 patients. The reduced CSF folate in 19 of these 23 patients could be explained by serum FR autoantibodies blocking the folate binding site of the membrane-attached FR on the choroid epithelial cells. Oral folinic acid supplements led to normal CSF 5MTHF and partial or complete clinical recovery after 12 months. Serum FR autoimmunity appears to represent an important factor in the pathogenesis of reduced folate transport to the nervous system among children with early-onset low-functioning autism associated with or without neurological deficits. Early detection of FR autoantibodies may be a key factor in the prevention and therapeutic intervention among this subgroup of patients with autism.
在两种自闭症谱系障碍中，即雷特综合征和伴有神经异常的婴儿低功能自闭症中，发现了叶酸向中枢神经系统转运减少的情况。对25例有或无神经功能缺损的早发性低功能自闭症患者进行了血清叶酸、脑脊液（CSF）5-甲基四氢叶酸（5MTHF）以及阻断型血清FR自身抗体的评估，以确定叶酸受体（FR）自身抗体在叶酸跨血脑屏障转运方面的意义。尽管血清叶酸正常，但25例患者中有23例脑脊液5MTHF水平较低。这23例患者中有19例脑脊液叶酸降低可由血清FR自身抗体阻断脉络丛上皮细胞膜附着的FR的叶酸结合位点来解释。口服亚叶酸补充剂12个月后可使脑脊液5MTHF恢复正常，并使临床症状部分或完全恢复。血清FR自身免疫似乎是早发性低功能自闭症患儿（无论有无神经功能缺损）中叶酸向神经系统转运减少的发病机制中的一个重要因素。早期检测FR自身抗体可能是该亚组自闭症患者预防和治疗干预的关键因素。
