对通过新生儿筛查发现的八名中国无症状甲基丙二酸血症患者进行生化、分子及预后分析。
Biochemical, molecular and outcome analysis of eight chinese asymptomatic individuals with methyl malonic acidemia detected through newborn screening.
作者信息
Han Lianshu, Wu Shengnan, Ye Jun, Qiu Wenjuan, Zhang Huiwen, Gao Xiaolan, Wang Yu, Gong Zhuwen, Jin Jing, Gu Xuefan
机构信息
Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Pediatric Endocrinology and Genetic Metabolism, Zhengzhou Children's Hospital, Henan, China.
出版信息
Am J Med Genet A. 2015 Oct;167A(10):2300-5. doi: 10.1002/ajmg.a.37147. Epub 2015 May 17.
Methyl malonic academia (MMA) is characterized by abnormal accumulation of methyl malonic acid in body fluids. Patients usually have a variety of clinical symptoms including recurrent vomiting, metabolic acidosis, developmental delay, seizure, or death. However, a few cases where the patients have no symptom are also reported. Here, we conducted clinical, biochemical, and molecular analysis of eight Chinese patients identified through newborn screening between 2003 and 2013. All the patients had significantly higher blood propionylcarnitine (C3) concentrations, ratio of propionylcarnitine/acetylcarnitine (C3/C2); and their urine methyl malonic acid and methylcitric acid (MCA) excretions were remarkably higher than normal at diagnosis and during follow-ups. In addition, five different known mutations were identified in seven of the eight patients in either MUT or MMACHC. All these mutations were expected to produce defective proteins that would result in decreased or even total loss of methyl malonyl-CoA mutase activity. However, normal outcomes were found in all patients in physical growth, intellectual performance and cerebral MRI analysis at diagnosis (range, 14-53 days) and during follow-ups (range, 1.8-10 years). Our study is the first report of Chinese MMA patients with increased secretion of methyl malonic acid and molecular defects in MUT or MMACHC yet remain asymptomatic.
甲基丙二酸血症(MMA)的特征是体液中甲基丙二酸异常蓄积。患者通常有多种临床症状,包括反复呕吐、代谢性酸中毒、发育迟缓、癫痫发作或死亡。然而,也有少数患者无症状的病例报道。在此,我们对2003年至2013年间通过新生儿筛查确定的8例中国患者进行了临床、生化和分子分析。所有患者的血液丙酰肉碱(C3)浓度、丙酰肉碱/乙酰肉碱比值(C3/C2)均显著升高;在诊断时及随访期间,他们尿液中的甲基丙二酸和甲基柠檬酸(MCA)排泄量明显高于正常水平。此外,在8例患者中的7例的MUT或MMACHC基因中鉴定出5种不同的已知突变。所有这些突变预计会产生有缺陷的蛋白质,导致甲基丙二酰辅酶A变位酶活性降低甚至完全丧失。然而,在诊断时(范围为14 - 53天)及随访期间(范围为1.8 - 10年),所有患者在体格生长、智力表现和脑部MRI分析方面均有正常结果。我们的研究是关于中国MMA患者甲基丙二酸分泌增加且MUT或MMACHC存在分子缺陷但仍无症状的首次报道。