Ding Yuan, Wang Qiao, Gong Chun-Xiu
Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Centre for Children's Health, Beijing 100045, P.R. China.
Med Int (Lond). 2022 Apr 5;2(2):12. doi: 10.3892/mi.2022.37. eCollection 2022 Mar-Apr.
Hyperhomocysteinemia is a common medical condition observed in patients with aminoaciduria. Deficiency in cystathionine beta-synthase, metabolism of cobalamin associated C, peroxiredoxin 1, 5-methyltetrahydrofolate-homocysteine methyltransferase reductase, LMBR1 domain containing 1, 5-methyltetrahydrofolate-homocysteine methyltransferase or 5,10-methylenetetrahydrofolate reductase () all can result in an elevation in plasma homocysteine, which has been reported to be a risk factor of vascular events, such as atherosis, acute myocardial infarction and cerebral stroke. Hyperhomocysteinemia due to the deficiency of 5,10-methylenetetrahydrofolate reductase (MTHFR; also known as 5,10-methyl THR reductase) is an autosomal recessive rare disease caused by defects in the gene. The clinical manifestations of this disorder are heterogeneous, ranging from asymptomatic to severe neurological disorders. However, hydrocephalus has seldomly been reported in patients with MTHFR deficiency. The present study thus describes a case of severe MTHFR deficiency in an infant, whose main manifestation was hydrocephalus. The clinical course and genotype of the patient were also examined. Specifically, a 4-month-old boy with hydrocephalus was admitted to hospital. Clinical examinations and genetic sequencing of the patient were performed to determine the probable causative factors. A physical examination revealed that the patient had developmental delay and progressive hydrocephalus. Amino acid analysis of the blood revealed an enhancement in serum homocysteine levels and a decrease in blood methionine and free carnitine levels. The organic acid levels in urine were normal. Therefore, he was diagnosed with hyperhomocysteinemia. Targeted next-generation sequencing was performed to determine the pathogenetic gene in this case. A paternal mutation c.1530G>A (p.K510K) and a maternal mutation c.233C>A (p.S78X) were identified. Previous experimental evidence indicated that these two mutations were all pathogenic; therefore, this patient was ultimately diagnosed with MTHFR deficiency. The patient in described herein study presented with severe progressive hydrocephalus in association with a delayed developmental milestone. According to the clinical and genetic tests, the patient was diagnosed with severe MTHFR deficiency. It thus is recommended that screening for metabolites and performing gene sequencing in infants presenting with undisclosed hydrocephalus.
高同型半胱氨酸血症是氨基酸尿症患者中常见的一种病症。胱硫醚β-合酶、钴胺素相关C代谢、过氧化物酶体增殖物激活受体1、5-甲基四氢叶酸-同型半胱氨酸甲基转移酶还原酶、含LMBR1结构域1、5-甲基四氢叶酸-同型半胱氨酸甲基转移酶或5,10-亚甲基四氢叶酸还原酶（）的缺乏均会导致血浆同型半胱氨酸升高，据报道，这是血管事件的一个危险因素，如动脉粥样硬化、急性心肌梗死和脑卒中等。由5,10-亚甲基四氢叶酸还原酶（MTHFR；也称为5,10-甲基THR还原酶）缺乏引起的高同型半胱氨酸血症是一种常染色体隐性罕见疾病，由基因缺陷所致。该疾病的临床表现具有异质性，从无症状到严重的神经系统疾病不等。然而，MTHFR缺乏症患者很少有脑积水的报道。因此，本研究描述了一名婴儿严重MTHFR缺乏症病例，其主要表现为脑积水。还对该患者的临床病程和基因型进行了检查。具体而言，一名患有脑积水的4个月大男孩入院。对该患者进行了临床检查和基因测序，以确定可能的致病因素。体格检查发现该患者发育迟缓且脑积水呈进行性加重。血液氨基酸分析显示血清同型半胱氨酸水平升高，血液蛋氨酸和游离肉碱水平降低。尿液中的有机酸水平正常。因此，他被诊断为高同型半胱氨酸血症。进行了靶向二代测序以确定该病例的致病基因。鉴定出一个父系突变c.1530G>A（p.K510K）和一个母系突变c.233C>A（p.S78X）。先前的实验证据表明这两个突变均具有致病性；因此，该患者最终被诊断为MTHFR缺乏症。本研究中描述的患者表现为严重的进行性脑积水，并伴有发育里程碑延迟。根据临床和基因检测，该患者被诊断为严重MTHFR缺乏症。因此，建议对出现不明原因脑积水的婴儿进行代谢物筛查和基因测序。
