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

Abstract

Importance

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.

Objective

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.

Data sources

MEDLINE, Embase, CRD, Cochrane Library, Scopus, CINAHL, and PROSPERO. Study Selection: All studies reporting the epidemiology characteristics of MMA were selected.

Data extraction and synthesis

Characteristics of study, subjects, and epidemiology were extracted, random-effect models were used for meta-analyses.

Main outcome and measure

Pooled prevalence of MMA.

Results

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.

Conclusions and relevance

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.

Keywords:

• Methylmalonic acidemia
• epidemiology
• newborns
• clinical-suspected
• meta-analyse

Acknowledgments

We are grateful for the kind help of ZhenNi Liu and ShaSha Wang in acquiring the full-text of the part of the literature.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This research was supported by the National Key Research and Development Program of China under Grant [2021YFC1005300].