Abstract：
Methionine adenosyltransferase I/III deficiency is an inborn error of metabolism due to mutations in the MAT1A gene. It is the most common cause of hypermethioninemia in newborn screening. Heterozygotes are often asymptomatic. In contrast, homozygous or compound heterozygous individuals can develop severe neurological symptoms. Less than 70 cases with biallelic variants have been reported worldwide. A methionine-restricted diet is recommended if methionine levels are above 500−600 µmol/L. In this study, we report on a female patient identified with elevated methionine concentrations in a pilot newborn screening program. The patient carries a previously described variant c.1132G>A (p.Gly378Ser) in homozygosity. It is located at the C-terminus of MAT1A. In silico analysis suggests impaired protein stability by β-turn disruption. On a methionine-restricted diet, her serum methionine concentration ranged between 49−605 µmol/L (median 358 µmol/L). Her clinical course was characterized by early-onset muscular hypotonia, mild developmental delay, delayed myelination and mild periventricular diffusion interference in MRI. At 21 months, the girl showed age-appropriate neurological development, but progressive diffusion disturbances in MRI. Little is known about the long-term outcome of this disorder and the necessity of treatment. Our case demonstrates that neurological symptoms can be transient and even patients with initial neurologic manifestations can show normal development under dietary management.
摘要：
甲硫氨酸腺苷转移酶I/III缺乏是由于MAT1A基因突变导致的先天性代谢错误。它是新生儿筛查中高蛋氨酸血症的最常见原因。杂合子通常无症状。相比之下,纯合或复合杂合个体可出现严重的神经症状。世界范围内报道了少于70例具有双等位基因变异的病例。如果蛋氨酸水平高于500-600µmol/L，建议使用蛋氨酸限制饮食。在这项研究中,我们报道了一名女性患者在一项试点新生儿筛查计划中发现甲硫氨酸浓度升高.患者携带先前描述的变体c.1132G>A（p。Gly378Ser）纯合性。它位于MAT1A的C端。计算机模拟分析表明，β-转角破坏会损害蛋白质的稳定性。在蛋氨酸限制饮食中，她的血清蛋氨酸浓度范围为49-605µmol/L(中位数358µmol/L).她的临床过程以早发性肌肉张力减退为特征，轻度发育迟缓,MRI中延迟髓鞘形成和轻度脑室周围弥散干扰。21个月时,这个女孩表现出与年龄相适应的神经发育，而是MRI中进行性扩散障碍。对这种疾病的长期结果和治疗的必要性知之甚少。我们的病例表明，神经系统症状可能是短暂的，即使具有初始神经系统表现的患者在饮食管理下也可以表现出正常的发育。
