Clinical outcomes of patients with mut-type methylmalonic acidemia identified through expanded newborn screening in China.

IF 3.8 3区 医学 Q2 GENETICS & HEREDITY Human Genomics Pub Date : 2024-07-29 DOI:10.1186/s40246-024-00646-0
Shiying Ling, Shengnan Wu, Ruixue Shuai, Yue Yu, Wenjuan Qiu, Haiyan Wei, Chiju Yang, Peng Xu, Hui Zou, Jizhen Feng, Tingting Niu, Haili Hu, Huiwen Zhang, Lili Liang, Yu Wang, Ting Chen, Feng Xu, Xuefan Gu, Lianshu Han
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Abstract

Background: Isolated methylmalonic acidemia, an autosomal recessive disorder of propionate metabolism, is usually caused by mutations in the methylmalonyl-CoA mutase gene (mut-type). Because no universal consensus was made on whether mut-type methylmalonic acidemia should be included in newborn screening (NBS), we aimed to compare the outcome of this disorder detected by NBS with that detected clinically and investigate the influence of NBS on the disease course.

Design & methods: In this study, 168 patients with mut-type methylmalonic acidemia diagnosed by NBS were compared to 210 patients diagnosed after disease onset while NBS was not performed. Clinical data of these patients from 7 metabolic centers in China were analyzed retrospectively, including initial manifestations, biochemical metabolites, the responsiveness of vitamin B12 therapy, and gene variation, to explore different factors on the long-term outcome.

Results: By comparison of the clinically-diagnosed patients, NBS-detected patients showed younger age at diagnosis, less incidence of disease onset, better responsiveness of vitamin B12, younger age at start of treatment, lower levels of biochemical features before and after treatment, and better long-term prognosis (P < 0.01). Onset of disease, blood C3/C2 ratio and unresponsiveness of vitamin B12 were more positively associated with poor outcomes of patients whether identified by NBS. Moreover, the factors above as well as older age at start of treatment were positively associated with mortality.

Conclusions: This research highly demonstrated NBS could prevent major disease-related events and allow an earlier treatment initiation. As a key prognostic factor, NBS is beneficial for improving the overall survival of infants with mut-type methylmalonic acidemia.

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中国通过扩大新生儿筛查发现的突变型甲基丙二酸血症患者的临床疗效。
背景:孤立型甲基丙二酸血症是一种常染色体隐性遗传的丙酸代谢紊乱,通常由甲基丙二酰-CoA突变酶基因(突变型)突变引起。由于对突变型甲基丙二酸血症是否应纳入新生儿筛查(NBS)尚未达成普遍共识,我们旨在比较NBS与临床发现的该疾病的结果,并研究NBS对病程的影响:在这项研究中,168 名通过 NBS 诊断的突变型甲基丙二酸血症患者与 210 名在发病后未进行 NBS 诊断的患者进行了比较。对这些患者来自中国 7 个代谢中心的临床数据进行回顾性分析,包括初始表现、生化代谢物、维生素 B12 治疗反应性和基因变异,以探讨影响长期预后的不同因素:结果:与临床诊断的患者相比,NBS检测出的患者诊断年龄更小、发病率更低、对维生素B12的反应性更好、开始治疗的年龄更小、治疗前后的生化特征水平更低、远期预后更好(P 结论:该研究高度证明了NBS可预防和治疗慢性乙型肝炎:这项研究高度证明了 NBS 可以预防重大疾病相关事件的发生,并能更早地开始治疗。作为一个关键的预后因素,NBS 有利于提高突变型甲基丙二酸血症婴儿的总体生存率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Human Genomics
Human Genomics GENETICS & HEREDITY-
CiteScore
6.00
自引率
2.20%
发文量
55
审稿时长
11 weeks
期刊介绍: Human Genomics is a peer-reviewed, open access, online journal that focuses on the application of genomic analysis in all aspects of human health and disease, as well as genomic analysis of drug efficacy and safety, and comparative genomics. Topics covered by the journal include, but are not limited to: pharmacogenomics, genome-wide association studies, genome-wide sequencing, exome sequencing, next-generation deep-sequencing, functional genomics, epigenomics, translational genomics, expression profiling, proteomics, bioinformatics, animal models, statistical genetics, genetic epidemiology, human population genetics and comparative genomics.
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