OBJECTIVES: Methylmalonic acidemia or aciduria (MMA) is a serious, life-threatening inherited metabolic disorder biochemically characterized by accumulation of methylmalonic acid primarily due to deficiency in methylmalonyl-CoA mutase (MUT). The prognosis is generally poor and management of the disorder is typically limited to diet restriction, other supportive measures, and liver and/or kidney transplant for severely affected individuals. A systematic literature review (SLR) was undertaken to assess and compile published epidemiological data on MMA with a focus on MMA caused by methylmalonyl-CoA mutase deficiency (OMIM #251000).

METHODS: The SLR was conducted in compliance with the PRISMA statement and covered Medline, Embase, Cochrane Database of Systematic Reviews, CRD, Academic Search Complete, CINAHL and PROSPERO databases. Websites of rare disease organizations were also searched for eligible studies.

RESULTS: Out of the 1114 identified records, 227 papers were assessed for eligibility in full text and finally, 66 articles were included into the qualitative synthesis. Newborn screening programs provided relatively precise estimates on the birth prevalence of MMA and its subtypes. The overall detection rates of MMA and isolated MMA were below 15 and 7 cases per 100,000 newborns, respectively. A tendency towards increased birth prevalence rates was observed in Southeast Asia and the region of Middle East and North Africa. The literature reporting on the epidemiology of MMA caused by MUT deficiency is scarce. Investigating studies with large sample size (>100,000), the overall detection rate for MMA due to MUT deficiency is lower than 1.7 per 100,000 newborns in all geographic regions with the exception of the Middle East.

CONCLUSIONS: Implementation of newborn screening in various countries has allowed the estimation of MMA and MMA MUT birth prevalence. Studies reporting point prevalence data were not identified. The conducted SLR clearly indicates that MMA and its subtypes, including MMA caused by MUT deficiency are rare indications.