The epidemiology of medium chain acyl-CoA dehydrogenase deficiency: An update

Abstract

The most common fatty acid oxidation disorder, medium chain acyl-CoA dehydrogenase deficiency (MCADD), has become the focal point for the adoption of tandem mass spectrometry to detect it and related inborn errors of metabolism. This article updates a human genome epidemiology review of MCADD published in 1999. The focus of this update is on epidemiologic parameters rather than mutations associated with MCADD. Currently available information from screening studies on the frequency of detection of MCADD in newborns, as well as the frequency of homozygotes for the common mutation in the ACADM gene, is summarized. In the United States, the average incidence of the disorder is from 1 in 15,000 to 1 in 20,000 births, with individual states reporting frequencies from 1 in 10,000 to 1 in 30,000 births. In addition, a systematic review was undertaken of the published literature on the frequency of mortality and developmental disabilities among children with MCADD, both in screened and unscreened cohorts. It seems that in the absence of newborn screening for MCADD, premature death or serious disability occurs in 20% to 25% of children with the disorder. Systematic collection and analysis of follow-up data are still needed to ascertain the frequencies of outcomes in screened cohorts.

Relevance of Expanded Neonatal Screening of Medium-Chain Acyl Co-A Dehydrogenase Deficiency: Outcome of a Decade in Galicia (Spain)

“…It has been reported that the incidence of MCADD is similar to that of phenylketonuria (1:10,000 live newborns) or even higher (Grosse et al 2006). In our population, the frequency is 1/18,847 live births.…”

Combined defects in oxidative phosphorylation and fatty acid β-oxidation in mitochondrial disease

“…MCAD deficiency (OMIM #201450) is the most well studied FAO disease [107], with the majority of symptomatic MCAD deficiencies thought to result from a common point mutation (985A>G) in ACADM [108]. Clinical presentations include hypotonia, Reye-like Syndrome, seizures, apnoea, hepatomegaly, fever, vomiting, diarrhoea and coma [109].…”

Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening

“…Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inborn error of fatty acid oxidation, which affects about 1:20,000 to 1:8,000 newborns (Andresen et al 2001;Grosse et al 2006;Saudubray et al 2012). It is included in many newborn screening programmes worldwide (National Newborn Screening and Genetics Resource Center, Austin, Texas; Bundesausschuss 2005; Wilcken et al 2007).…”