Prevalence of methylmalonic acidemia among newborns and the clinical-suspected population: a meta-analyse

Knowing the scale of rare inborn errors is important for screening and resource allocation. Evidence on the prevalence of methylmalonic acidemia (MMA) among newborns and the clinical-suspected population from large-scale screening programs needs to be systematically synthesized. To estimate the worldwide prevalence of MMA for newborns and the clinical-suspected population and explore the differences in different regions, periods, and diagnostic technologies. MEDLINE, Embase, CRD, Cochrane Library, Scopus, CINAHL, and PROSPERO. Study Selection: All studies reporting the epidemiology characteristics of MMA were selected. Characteristics of study, subjects, and epidemiology were extracted, random-effect models were used for meta-analyses. Pooled prevalence of MMA. This study included 111 studies. The pooled prevalence of MMA worldwide was 1.14 per 100,000 newborns (1516/190,229,777 newborns, 95% CI: 0.99–1.29) and 652.11 per 100,000 clinical-suspected patients (1360/4,805,665 clinical-suspected individuals, CI: 544.14–760.07). Asia and Africa got a higher pooled prevalence of MMA. The prevalence of MMA in newborns increased through the years, while that in the clinical-suspected population decreased. Collecting blood ≥ 72 h after birth had a higher pooled prevalence of MMA than collecting during 24 h–72 h after birth. The combining-use of MS/MS and GC/MS had a higher pooled prevalence than the single-use of MS/MS or GC/MS. Prevalence of cbl C, mut, cbl B, cbl A, isolated MMA, combined MMA and homocystinuria, vitamin B12-responsive MMA was synthesized. Prevalence of MMA among newborns was extremely low, but considerably high in the clinical-suspected population, indicating the need for more efficient newborn screening strategies and closer monitoring of the high-risk population for the early signs of MMA. Asia and Africa should attach importance to the high prevalence of MMA. Further diagnostic tests were recommended for the combining-use vs single-use of MS/MS and GC/MS and for collecting blood after 72 h vs during 24–72 h after birth.

明确罕见先天性代谢异常的发病规模，对于疾病筛查与资源配置具有重要意义。目前亟需系统整合大型筛查项目中关于新生儿及临床疑似人群中甲基丙二酸血症（methylmalonic acidemia, MMA）的流行病学证据。本研究旨在估算全球范围内新生儿与临床疑似人群中MMA的流行率，并探究不同地区、研究时段及诊断技术下的流行率差异。检索数据库包括MEDLINE、Embase、CRD、Cochrane Library、Scopus、CINAHL及PROSPERO。研究筛选：纳入所有报道MMA流行病学特征的相关研究。提取研究对象、研究特征及流行病学相关数据，并采用随机效应模型进行荟萃分析，主要结局指标为MMA的合并流行率。本研究共纳入111项相关研究。全球范围内新生儿MMA的合并流行率为1.14/10万（1516/190229777名新生儿，95%置信区间：0.99~1.29）；临床疑似人群中MMA的合并流行率则为652.11/10万（1360/4805665名疑似个体，95%置信区间：544.14~760.07）。亚洲与非洲地区的MMA合并流行率更高。新生儿MMA的流行率随研究年份推移呈上升趋势，而临床疑似人群的MMA流行率则呈下降趋势。出生后72小时及以上采血的新生儿MMA合并流行率，高于出生后24~72小时采血的人群。串联质谱（MS/MS）与气相色谱-质谱联用（GC/MS）联合检测的MMA合并流行率，高于单独使用MS/MS或单独使用GC/MS的情况。本研究还整合了cbl C型、mut型、cbl B型、cbl A型、孤立性MMA、合并同型半胱氨酸血症的MMA以及维生素B12反应型MMA的流行率数据。新生儿MMA流行率极低，但临床疑似人群的MMA流行率却显著偏高，这提示亟需优化新生儿筛查策略，并加强对高危人群的密切监测以及时发现MMA早期征象。亚洲与非洲地区应重视当地较高的MMA流行现状。研究建议针对MS/MS与GC/MS联合检测vs单独检测、出生72小时后采血vs24~72小时采血这两种情况开展进一步诊断试验以明确差异。