甲基丙二酸血症合并 MMACHC 和 MUT 基因突变的临床和脑电图特征。

Clinical and electroencephalogram characteristics of methylmalonic acidemia with MMACHC and MUT gene mutations.

机构信息

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

BMC Pediatr. 2024 Feb 14;24(1):119. doi: 10.1186/s12887-024-04559-8.

DOI:10.1186/s12887-024-04559-8

PMID:38355526

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10865547/

Abstract

OBJECTIVE

This study investigated the clinical, imaging, and electroencephalogram (EEG) characteristics of methylmalonic acidemia (MMA) with nervous system damage as the primary manifestation.

METHODS

From January 2017 to November 2022, patients with nervous system injury as the main clinical manifestation, diagnosed with methylmalonic acidemia by metabolic and genetic testing, were enrolled and analyzed. Their clinical, imaging, and electroencephalogram data were analyzed.

RESULTS

A total of 18 patients were enrolled, including 15 males and 3 females. The clinical symptoms were convulsions, poor feeding, growth retardation, disorder of consciousness, developmental delay, hypotonia, and blood system changes. There were 6 cases (33%) of hydrocephalus, 9 (50%) of extracerebral space widened, 5 (27%) of corpus callosum thinning, 3 (17%) of ventricular dilation, 3 (17%) of abnormal signals in the brain parenchyma (frontal lobe, basal ganglia region, and brain stem), and 3 (17%) of abnormal signals in the lateral paraventricular. In addition, there were 3 cases (17%) of cerebral white matter atrophy and 1 (5%) of cytotoxic edema in the basal ganglia and cerebral peduncle. EEG data displayed 2 cases (11%) of hypsarrhythmia, 3 (17%) of voltage reduction, 12(67%) of abnormal discharge, 13 (72%) of abnormal sleep physiological waves or abnormal sleep structure, 1 (5%) of immature (delayed) EEG development, and 8 (44%) of slow background. There were 2 cases (11%) of spasms, 1 (5%) of atonic seizures, and 1 (5%) of myoclonic seizures. There were 16 patients (89%) with hyperhomocysteinemia. During follow-up, 1 patient was lost to follow-up, and 1 died. In total, 87.5% (14/16) of the children had varying developmental delays. EEG was re-examined in 11 cases, of which 8 were normal, and 3 were abnormal. Treatments included intramuscular injections of vitamin B12, L-carnitine, betaine, folic acid, and oral antiepileptic therapy. Acute treatment included anti-infective, blood transfusion, fluid replacement, and correcting acidosis. The other treatments included low-protein diets and special formula milk powder.

CONCLUSION

Methylmalonic acidemia can affect the central nervous system, leading to structural changes or abnormal signals on brain MRI. Metabolic screening and genetic testing help clarify the diagnosis. EEG can reflect changes in brain waves during the acute phase.

摘要

目的

本研究旨在探讨以神经系统损伤为主要表现的甲基丙二酸血症（MMA）的临床、影像学和脑电图（EEG）特征。

方法

自 2017 年 1 月至 2022 年 11 月，我们纳入了以神经系统损伤为主要临床表现、经代谢和基因检测诊断为甲基丙二酸血症的患者，并对其临床、影像学和脑电图数据进行了分析。

结果

共纳入 18 例患者，其中男性 15 例，女性 3 例。临床表现为抽搐、喂养困难、生长迟缓、意识障碍、发育迟缓、肌张力低下、血液系统改变。6 例（33%）患者存在脑积水，9 例（50%）存在颅外间隙增宽，5 例（27%）存在胼胝体变薄，3 例（17%）存在脑室扩张，3 例（17%）存在脑实质（额叶、基底节区和脑干）异常信号，3 例（17%）存在侧脑室旁异常信号。此外，3 例（17%）患者存在脑白质萎缩，1 例（5%）患者存在基底节区和大脑脚细胞毒性水肿。脑电图数据显示 2 例（11%）存在高度失律，3 例（17%）存在电压降低，12 例（67%）存在异常放电，13 例（72%）存在异常睡眠生理波或异常睡眠结构，1 例（5%）存在不成熟（延迟）脑电图发育，8 例（44%）存在背景活动减慢。2 例（11%）存在痉挛发作，1 例（5%）存在失张力发作，1 例（5%）存在肌阵挛发作。16 例（89%）患者存在高同型半胱氨酸血症。随访期间，1 例患者失访，1 例死亡。共有 14 例（89%）患儿存在不同程度的发育迟缓。11 例患儿复查脑电图，其中 8 例正常，3 例异常。治疗包括肌内注射维生素 B12、左卡尼汀、甜菜碱、叶酸和口服抗癫痫治疗。急性治疗包括抗感染、输血、补液和纠正酸中毒。其他治疗包括低蛋白饮食和特殊配方奶粉。