戊二酸血症Ⅰ型的临床表现、影像学特点、治疗及随访  

Clinical manifestations, neuroimaging features, treatment, and follow-up in four pediatric patients withglutaric aciduria typeⅠ

作　　者：刘琦[1] 夏蝉[1] 陈伟[2] 叶万定 陈益平[1] 

机构地区：[1]温州医科大学附属第二医院儿童感染科,浙江温州325027 [2]温州医科大学附属第二医院放射科,浙江温州325027

出　　处：《中华临床营养杂志》2017年第1期40-46,共7页Chinese Journal of Clinical Nutrition

摘　　要：目的 探讨戊二酸血症Ⅰ型（GA-1）患儿的临床表现、影像学特点、治疗及随访。方法 对我院2010至2016年收治及随访的4例GA-1患儿给予特殊奶粉、左旋肉碱及维生素B2治疗。随访4～5年定期行头颅磁共振成像检查、血串联质谱、生长发育指标监测、智力发育测试及基因检测。结果 4例患儿分别在生后2、13、4、7个月确诊GA-1，3例确诊前出现惊厥，治疗后均无惊厥再发。4例在T2加权成像均出现额颞叶萎缩、额颞部蛛网膜下腔明显增宽，弥散加权成像见双侧苍白球呈对称性高信号影。经随访可见磁共振成像表现逐渐好转，双侧额颞顶部脑外间隙明显较前缩小。对治疗效果进行评估，定期通过滤干纸片血串联质谱法对戊二酰肉碱（C5DC）及C5DC/辛酰肉碱（C8）进行监测，4例患儿C5DC、C5DC/C8检测均高于正常值范围，其中病例3偏离严重。4例患儿随访体质量在－2 SD～0，身高在－1 SD～0。智力发育测试中病例1、4为智力轻度异常，病例2、3为极重度智力残疾。基因检测证实4例患儿存在基因突变，其中病例1、3、4为IVS10 -2A＞C纯合突变，病例2为［IVS10 -2A＞C］＋［c.245G＞c（p.Arg82Pro）］杂合突变。2例女患儿正常入幼儿园，2例男患儿运动发育落后、痉挛性瘫痪不能独力行走。结论 GA-1患者的临床型与基因型无明显相关性；新生儿筛查是早期发现患者的关键。Objective To investigate the clinical features, magnetic resonance imaging（MRI）, treatment, and follow-up of patients with glutaric aciduria type Ⅰ （GA-1）.Methods Four pediatric patients with GA-1 diagnosed in our hospital were included in this study. They were treated with special diets and carnitine supplements. MRI and tandem mass spectrometry （MS/MS） were performed, and the mental development indices were measured. Results GA-1 was confirmed 2 months, 13 months, 4 months, and 7 months after birth. Seizure had been observed before the disease diagnosis in three patients and disappeared after treatment. In all four patients, T2-weighted brain MRI showed frontotemporal atrophy or hypoplasia and enlarged subarachnoid space in the sylvian fissures and anterior to the temporal lobes. Diffusion weighted imaging revealed high-density lesions over both the putamen and globus pallidus. The patients were followed up for 4 to 5 years. Plasma amino acids and acylcarnitine profile were monitored every 3-5 months. The mean C5DC level and C5DC/C8 were kept the higher limits of the normal ranges, especially in case 3. During the follow-up, the body weight was at -2 SD-0 and the height at -1 SD-0. Intellectual development test showed that case 1 and case 4 had mildly abnormal intelligence, whereas case 2 and case 3 had extremely severe intellectual disability. Gene test confirmed the presence of gene mutations in all four cases, including IVS10 -2A〉C homozygous mutation in cases 1, 3, and 4 and [IVS10 -2A〉C]＋[c.245G〉c（p.Arg82Pro）] hybrid mutation in case 2.Two female children were smoothly enrolled by local kindergarten, while two male children were unable to walk alone due to delayed motor development and spastic paralysis. Conclusions The phenotype of GA-1 patients is not remarkably correlated with its genotype correlation. Newborn screening is essential for identifying GA-1 patients.

关 键 词：戊二酸血症Ⅰ型 磁共振成像 随访 智力 治疗 

分 类 号：R725.9[医药卫生—儿科]