亚甲基四氢叶酸还原酶（MTHFR）基因杂合性缺失导致高同型半胱氨酸血症性脑静脉血栓形成：病例报告。

Cerebral venous thrombosis with hyperhomocysteinemia due to loss of heterozygosity at methylenetetrahydrofolate reductase (MTHFR) locus: a case report.

机构信息

Department of Neurology, The First Medical Center, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, PR China.

Brain Science Center, Tsinghua University Yuquan Hospital, No. 5 Shijingshan Road, Beijing, 100049, PR China.

出版信息

BMC Neurol. 2023 Apr 19;23(1):154. doi: 10.1186/s12883-023-03200-y.

DOI:10.1186/s12883-023-03200-y

PMID:37076800

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10114475/

Abstract

BACKGROUND

Loss of heterozygosity (LOH) at methylenetetrahydrofolate reductase (MTHFR) locus has been reported in tumor tissue. But the mutation was never reported in cerebral venous thrombosis (CVT) with hyperhomocysteinemia (HHcy) before.

CASE PRESENTATION

A 14-year-old girl was admitted with an intermittent headache and nausea for 2 months. The plasma homocysteine level was 77.2 µmol/L. Lumbar puncture revealed an intracranial pressure > 330 mmH2O. Cerebral MRI and MRV revealed superior sagittal sinus thrombosis. Whole-exome sequencing revealed LOH at Chr1:11836597-11,867,232 affects exons 10-21 of C1orf167, the entire MTHFR, and exons 1-2 of the CLCN6 gene. The normal allele was the c.665 C > T/677 C > T variant in MTHFR. The patient was treated with nadroparin for 2 weeks, followed by oral rivaroxaban. Supplemental folate and vitamins B12 and B6 were prescribed. One month later, she had no headache and the intracranial pressure had decreased to 215 mmH2O. MRI showed shrinkage of the thrombosis in the superior sagittal sinus, the degree of stenosis had significantly decreased.

CONCLUSIONS

Rare LOH at the MTHFR locus should be analyzed in CVT with HHcy. With anticoagulation treatment, the prognosis was good.

摘要

背景

亚甲基四氢叶酸还原酶（MTHFR）基因座的杂合性缺失（LOH）已在肿瘤组织中报道。但在此之前，从未在伴有高同型半胱氨酸血症（HHcy）的脑静脉血栓形成（CVT）中报道过该突变。

病例介绍

一名 14 岁女孩因间歇性头痛和恶心 2 个月入院。血浆同型半胱氨酸水平为 77.2 µmol/L。腰椎穿刺显示颅内压>330 mmH2O。脑 MRI 和 MRV 显示上矢状窦血栓形成。全外显子组测序显示 Chr1:11836597-11,867,232 处 LOH 影响 C1orf167 的外显子 10-21、整个 MTHFR 和 CLCN6 基因的外显子 1-2。正常等位基因是 MTHFR 中的 c.665 C > T/677 C > T 变体。患者接受那屈肝素治疗 2 周，随后口服利伐沙班。开了叶酸、维生素 B12 和 B6 进行补充。一个月后，她没有头痛，颅内压已降至 215 mmH2O。MRI 显示上矢状窦血栓缩小，狭窄程度明显降低。