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Meta-Analysis
. 2019 Apr 25;14(1):84.
doi: 10.1186/s13023-019-1063-z.

Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency

Tímea Almási  1 , Lin T Guey  2 , Christine Lukacs  2 , Kata Csetneki  3 , Zoltán Vokó  3   4 , Tamás Zelei  3
Affiliations
Meta-Analysis

Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency

Tímea Almási et al. Orphanet J Rare Dis. .

Abstract

Methylmalonic acidemia/aciduria (MMA) is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid. Isolated MMA is primarily caused by the deficiency of methylmalonyl-CoA mutase (MMA mut; EC 5.4.99.2). A systematic literature review and a meta-analysis were undertaken to assess and compile published epidemiological data on MMA with a focus on the MMA mut subtype (OMIM #251000). Of the 1114 identified records, 227 papers were assessed for eligibility in full text, 48 articles reported on disease epidemiology, and 39 articles were included into the quantitative synthesis. Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. Meta-analysis pooled point estimates of MMA (all types) detection rates were 0.79, 1.12, 1.22 and 6.04 per 100,000 newborns in Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. The detection rate of isolated MMA was < 1 per 100,000 newborns in all regions with the exception of MENA where it approached 6 per 100,000 newborns. Few studies published data on the epidemiology of MMA mut, therefore no meta-analysis could have been performed on this subtype. Most of the identified papers reported birth prevalence estimates below 1 per 100,000 newborns for MMA mut. The systematic literature review clearly demonstrates that MMA and its subtypes are ultra-rare disorders.

Keywords: Epidemiology; Inherited metabolic disorder; Meta-analysis; Methylmalonic acidemia/aciduria; Methylmalonyl-CoA mutase deficiency; Newborn screening.

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Conflict of interest statement

Ethics approval and consent to participate

The study being a systematic review and meta-analysis is based on secondary analysis of already published data.

Consent for publication

Not applicable.

Competing interests

Tímea Almási, Tamás Zelei, Kata Csetneki, and Zoltán Vokó are employees of Syreon Research Institute and performed contracted research for Moderna, Inc. Lin T. Guey and Christine Lukacs are employees of Moderna, Inc. and receive salary and stock options as compensation for their employment. Nonetheless, the content of this paper, as well as the views and opinions expressed therein are those of the Authors and not the organizations that employ them.

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Figures

Fig. 1
Fig. 1
Flow of information diagram
Fig. 2
Fig. 2
Estimates on birth prevalence of methylmalonic acidemia. *Cumulative incidence in birth cohort; **Lifetime risk at birth, calculated by diagnosis (DX) method; DNK: Denmark; FRO: Faroe Islands; GRL: Greenland, NBS: Newborn Screening
Fig. 3
Fig. 3
Estimates on birth prevalence of methylmalonic acidemias caused by mutase deficiency. *Cumulative incidence in birth cohort; **Lifetime risk at birth, calculated by diagnosis (DX) method; DNK: Denmark; FRO: Faroe Islands; GRL: Greenland
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