测定儿童脑脊液中 5-甲基四氢叶酸及其在叶酸转运和代谢缺陷中的应用。

Determination of CSF 5-methyltetrahydrofolate in children and its application for defects of folate transport and metabolism.

机构信息

Department of Child Neurology, Okayama University Hospital, Okayama, Japan.

出版信息

Clin Chim Acta. 2016 Sep 1;460:120-5. doi: 10.1016/j.cca.2016.06.032. Epub 2016 Jun 27.

DOI:10.1016/j.cca.2016.06.032

PMID:27363740

Abstract

OBJECTIVE

To describe an assay of 5-methyltetrahydrofolate (5MTHF) in the cerebrospinal fluid (CSF) of children, to determine reference values, and to report the clinical significance of this assay in metabolic disorders affecting folate transport and metabolism.

METHODS

CSF 5MTHF was determined by high-performance liquid chromatography with fluorescent detection in pediatric patients including one with FOLR1 gene mutation and one with methylenetetrahydrofolate reductase (MTHFR) deficiency. CSF total folate was measured using an automated analyzer.

RESULTS

5MTHF and total folate were determined in 188 and 93 CSF samples, respectively. CSF 5MTHF was high throughout the first six months of life and subsequently declined with age. Reference values of CSF 5MTHF and total folate were determined from 162 and 82 samples, respectively. The patient with FOLR1 gene mutation had extremely low CSF 5MTHF and total folate, though these values normalized after folinic acid supplementation. The patient with MTHFR deficiency had extremely low 5MTHF and moderately low total folate; these values were not associated and showed no significant change after folic acid supplementation.

CONCLUSIONS

This 5MTHF assay is simple, rapid, sensitive, reliable, and cost-effective. It will aid in the diagnosis and therapeutic monitoring of metabolic disorders affecting folate transport and metabolism.

摘要

目的

描述一种测定儿童脑脊液（CSF）中 5-甲基四氢叶酸（5MTHF）的方法，确定参考值，并报告该方法在影响叶酸转运和代谢的代谢性疾病中的临床意义。

方法

采用高效液相色谱-荧光检测法测定包括 1 例 FOLR1 基因突变和 1 例亚甲基四氢叶酸还原酶（MTHFR）缺乏症患儿在内的儿科患者 CSF 中的 5MTHF。采用自动分析仪测定 CSF 总叶酸。

结果

分别测定了 188 份和 93 份 CSF 样本中的 5MTHF 和总叶酸。CSF 5MTHF 在生命的前六个月一直很高，随后随年龄下降。从 162 份和 82 份样本中确定了 CSF 5MTHF 和总叶酸的参考值。FOLR1 基因突变患者的 CSF 5MTHF 和总叶酸极低，但在补充叶酸后这些值恢复正常。MTHFR 缺乏症患者的 5MTHF 极低，总叶酸中度降低；这些值没有相关性，在补充叶酸后没有显著变化。