Munoz Tatiana, Patel Jinesh, Badilla-Porras Ramses, Kronick Jonathan, Mercimek-Mahmutoglu Saadet
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada; Genetics and Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Canada.
Brain Dev. 2015 Jan;37(1):168-70. doi: 10.1016/j.braindev.2014.03.003. Epub 2014 Apr 13.
Severe methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessively inherited inborn error of folate metabolism. We report a new patient with severe MTHFR deficiency who presented at age 4 months with early onset severe scoliosis associated with severe hypotonia. Markedly decreased MTHFR enzyme activity (0.3 nmoles CHO/mg protein/h; reference range>9) and compound heterozygous mutations (c. 1304T>C; p.Phe435Ser and c.1539dup; p.Glu514Argfs∗24) in the MTHFR gene confirmed the diagnosis. She was treated with vitamin B12, folic acid and betaine supplementation and showed improvements in her developmental milestones and hypotonia. To the best of our knowledge, this is the first patient with MTHFR deficiency reported with severe early onset scoliosis. Despite the late diagnosis and treatment initiation, she showed favorable short-term neurodevelopmental outcome. This case suggests that homocysteine measurement should be included in the investigations of patients with developmental delay, hypotonia and scoliosis within first year of life prior to organizing genetic investigations.
严重亚甲基四氢叶酸还原酶（MTHFR）缺乏症是一种罕见的常染色体隐性遗传的叶酸代谢先天性缺陷。我们报告了一名新的严重MTHFR缺乏症患者，该患者在4个月大时出现早发性严重脊柱侧弯并伴有严重肌张力减退。MTHFR酶活性显著降低（0.3纳摩尔CHO/毫克蛋白/小时；参考范围>9）以及MTHFR基因中的复合杂合突变（c.1304T>C；p.Phe435Ser和c.1539dup；p.Glu514Argfs∗24）证实了诊断。她接受了维生素B12、叶酸和甜菜碱补充治疗，其发育里程碑和肌张力减退情况有所改善。据我们所知，这是首例报告的伴有严重早发性脊柱侧弯的MTHFR缺乏症患者。尽管诊断和治疗开始较晚，但她的短期神经发育结果良好。该病例表明，在进行基因检测之前，对于1岁以内有发育迟缓、肌张力减退和脊柱侧弯的患者，应在检查中包括同型半胱氨酸检测。
