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

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. Electronic supplementary material The online version of this article (10.1186/s13023-019-1063-z) contains supplementary material, which is available to authorized users.

Second-Generation Pharmacological Chaperones: Beyond Inhibitors

“…The estimated incidence of MMA is 1:50,000 to 1:100,000 people. The portion of MMA attributed to cblB type is ~13% [ 113 ]. ATR is a mitochondrial enzyme involved in coenzyme B12 metabolism.…”

A rare mutation c.1663G > A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

“…Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. A recent global large size systematic literature review exposed that estimates of MMA (all types) detection rates were 1/126,582, 1/81,967, 1/81,967, and 1/16,556 newborns in Asia–Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively [ 3 ]. The incidence of MMA in China varies significantly from region to region and was reported to be 1/38,667 in Shanghai [ 4 ], 1/46,531 in Zhejiang province [ 5 ], 1/6,032 in Henan province [ 6 ], 1/40,166 in Jiangsu Suzhou district [ 7 ], 1/16,883 in Jiangsu Xuzhou district [ 8 ] and 1/5589 in Shandong Jining district [ 9 ].…”

A rare mutation c.1663G&gt;A (p.A555T) in the MMUT gene associated with mild clinical and biochemical phenotypes of methylmalonic acidemia in 30 Chinese patients

“…Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. A recent global large size systematic literature review exposed that estimates of MMA (all types) detection rates were 1/126,582, 1/81967, 1/81967, and 1/16556 newborns in Asia-Paci c, Europe, North America and the Middle East and North Africa (MENA) regions, respectively [3]. The incidence of MMA in China varies signi cantly from region to region and was reported to be 1/38,667 in Shanghai [4], 1/46,531 in Zhejiang province [5], 1/6,032 in Henan province [6], 1/40166 in Jiangsu Suzhou district [7], 1/16,883 in Jiangsu Xuzhou district [8] and 1/5589 in Shandong Jining district [9].…”

“…According to the biochemical manifestation, MMA can be classi ed into two common types: isolated MMA and MMA combined with homocysteinemia. The incidence of isolated MMA was <1/100,000 newborns in all regions worldwide with the exception of MENA where it approached 6/100,000 newborns [3]. In China, isolated MMA accounts for generally 30% of all types of MMA [5,8,9].…”