Gene: ACADM

Alternate names for this Gene: ACAD1|MCAD|MCADH

Gene Summary: This gene encodes the medium-chain specific (C4 to C12 straight chain) acyl-Coenzyme A dehydrogenase. The homotetramer enzyme catalyzes the initial step of the mitochondrial fatty acid beta-oxidation pathway. Defects in this gene cause medium-chain acyl-CoA dehydrogenase deficiency, a disease characterized by hepatic dysfunction, fasting hypoglycemia, and encephalopathy, which can result in infantile death. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Gene is located in Chromosome: 1

Location in Chromosome : 1p31.1

Description of this Gene: acyl-CoA dehydrogenase medium chain

Type of Gene: protein-coding

rs12126607 in ACADM gene and Glycine measurement PMID 31070104 2019 Genetic Determinants of Circulating Glycine Levels and Risk of Coronary Artery Disease.

PMID 30837465 2019 Assessing the causal association of glycine with risk of cardio-metabolic diseases.

rs1146586 in ACADM gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs1057516278 in ACADM gene and Medium-chain acyl-coenzyme A dehydrogenase deficiency PMID 23028790 2012 Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants.

PMID 22630369 2012 Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: data from a cohort study.

PMID 25940036 2015 Medium-Chain Acyl-CoA Dehydrogenase Deficiency: Evaluation of Genotype-Phenotype Correlation in Patients Detected by Newborn Screening.

PMID 11349232 2001 Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency.

PMID 9158144 1997 The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype?

PMID 20437613 2010 Mutations of a country: a mutation review of single gene disorders in the United Arab Emirates (UAE).

PMID 24294134 2013 Medium-chain acyl-CoA deficiency: outlines from newborn screening, in silico predictions, and molecular studies.

PMID 21483992 2011 New and known mutations associated with inborn errors of metabolism in a heterogeneous Middle Eastern population.

PMID 28581210 2017 Reduced cell surface levels of GPI-linked markers in a new case with PIGG loss of function.

PMID 20036593 2010 Lack of genotype-phenotype correlations and outcome in MCAD deficiency diagnosed by newborn screening in New York State.

PMID 15171998 2004 Rapid, comprehensive screening of the human medium chain acyl-CoA dehydrogenase gene.

PMID 16121256 2005 Medium-chain acyl-CoA dehydrogenase deficiency in gene-targeted mice.

PMID 20434380 2010 Allelic diversity in MCAD deficiency: the biochemical classification of 54 variants identified during 5 years of ACADM sequencing.

PMID 2251268 1990 Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency.

PMID 11409868 2001 Molecular and functional characterisation of mild MCAD deficiency.

PMID 1363805 1992 Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene.

PMID 10767181 2000 Identification of a novel mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency.

PMID 16291504 2006 Medium-chain acyl-CoA dehydrogenase deficiency: genotype-biochemical phenotype correlations.

PMID 11486912 2001 Compound heterozygosity in four asymptomatic siblings with medium-chain acyl-CoA dehydrogenase deficiency.

PMID 2394825 1990 Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation.

PMID 15832312 2005 Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency.

PMID 1671131 1991 Frequency of the G985 MCAD mutation in the general population.

PMID 1684086 1991 Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain Acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency.

PMID 23798014 2013 Neuropsychological outcomes in fatty acid oxidation disorders: 85 cases detected by newborn screening.

PMID 2393404 1990 Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency.

PMID 22848008 2012 Medium chain acyl-CoA dehydrogenase deficiency detected among Hispanics by New Jersey newborn screening.

PMID 24966162 2014 Functional studies of 18 heterologously expressed medium-chain acyl-CoA dehydrogenase (MCAD) variants.

PMID 7929823 1994 A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death.

PMID 22542437 2012 MCAD deficiency in Denmark.

PMID 7603790 1995 Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies.

PMID 9882619 1999 Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site.

PMID 8198141 1994 Disease-causing mutations in exon 11 of the medium-chain acyl-CoA dehydrogenase gene.

PMID 1902818 1991 Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli.

PMID 7929823 1994 Four compound heterozygote individuals from two unrelated families with A985G on one allele and a novel G to A mutation at nucleotide 583 (G583A) as the second mutant allele presented with MCAD deficiency in the first week of life.

PMID 21083904 2010 The first three years of screening for medium chain acyl-CoA dehydrogenase deficiency (MCADD) by newborn screening ontario.

PMID 18241067 2008 Novel mutations causing medium chain acyl-CoA dehydrogenase deficiency: under-representation of the common c.985 A > G mutation in the New York state population.

PMID 22975760 2013 An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.

PMID 19224950 2009 Protein misfolding is the molecular mechanism underlying MCADD identified in newborn screening.

PMID 15479234 2004 The Y42H mutation in medium-chain acyl-CoA dehydrogenase, which is prevalent in babies identified by MS/MS-based newborn screening, is temperature sensitive.

PMID 24718418 2014 The domain-specific and temperature-dependent protein misfolding phenotype of variant medium-chain acyl-CoA dehydrogenase.

PMID 23509891 2013 In vitro and in vivo consequences of variant medium-chain acyl-CoA dehydrogenase genotypes.

PMID 18188679 2008 Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: the importance of enzyme analysis to ascertain true MCAD deficiency.

PMID 20434380 2010 Here, we describe the classification of genotypes harboring at least one VUS through the comparison of C8 and HG values measured in individuals who are carriers of, or affected with, MCAD deficiency on the basis of the following genotypes: c.985A>G/wildtype, c.199T>C/c.985A>G and c.985A>G/c.985A>G.

PMID 26947917 2016 Significance of ACADM mutations identified through newborn screening of MCAD deficiency in Japan.

PMID 22166308 2011 Newborn screening for medium chain acyl-CoA dehydrogenase deficiency in England: prevalence, predictive value and test validity based on 1.5 million screened babies.

PMID 19780764 2009 Dissection of biochemical borderline phenotypes in carriers and genetic variants of medium-chain acyl-CoA dehyrogenase deficiency: implications for newborn screening [corrected].

PMID 21704015 2011 Quantitative liquid chromatography coupled with tandem mass spectrometry analysis of urinary acylglycines: application to the diagnosis of inborn errors of metabolism.

PMID 22683754 2012 Characterization of the molecular spectrum of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in a Greek newborns cohort: identification of a novel variant.

PMID 17273963 2007 Seemingly neutral polymorphic variants may confer immunity to splicing-inactivating mutations: a synonymous SNP in exon 5 of MCAD protects from deleterious mutations in a flanking exonic splicing enhancer.

PMID 6434827 1984 A new patient with dicarboxylic aciduria suggestive of medium-chain Acyl-CoA dehydrogenase deficiency presenting as Reye's syndrome.

PMID 27308838 2017 Variants of uncertain significance in newborn screening disorders: implications for large-scale genomic sequencing.

PMID 23829193 2014 Retrospective study of the medium-chain acyl-CoA dehydrogenase deficiency in Portugal.

PMID 18075239 2007 Acylcarnitine profiles during carnitine loading and fasting tests in a Japanese patient with medium-chain acyl-CoA dehydrogenase deficiency.

PMID 21239873 2011 Clinical, biochemical and genetic analyses in two Korean patients with medium-chain acyl-CoA dehydrogenase deficiency.

PMID 1729890 1992 Identification of a new mutation in medium-chain acyl-CoA dehydrogenase (MCAD) deficiency.

PMID 1356169 1992 Molecular basis of inherited medium-chain acyl-CoA dehydrogenase deficiency causing sudden child death.

PMID 7730333 1995 Effects of two mutations detected in medium chain acyl-CoA dehydrogenase (MCAD)-deficient patients on folding, oligomer assembly, and stability of MCAD enzyme.

PMID 8535441 1995 Comparison between medium-chain acyl-CoA dehydrogenase mutant proteins overexpressed in bacterial and mammalian cells.

PMID 19649258 2009 A novel tandem mass spectrometry method for rapid confirmation of medium- and very long-chain acyl-CoA dehydrogenase deficiency in newborns.

PMID 8102510 1993 A rare disease-associated mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene changes a conserved arginine, previously shown to be functionally essential in short-chain acyl-CoA dehydrogenase (SCAD).

PMID 24623196 2014 Experimental evidence for protein oxidative damage and altered antioxidant defense in patients with medium-chain acyl-CoA dehydrogenase deficiency.

PMID 18450854 2008 Spectrum of medium-chain acyl-CoA dehydrogenase deficiency detected by newborn screening.

PMID 23810226 2014 A synonymous polymorphic variation in ACADM exon 11 affects splicing efficiency and may affect fatty acid oxidation.

PMID 19064330 2009 A novel molecular aspect of Japanese patients with medium-chain acyl-CoA dehydrogenase deficiency (MCADD): c.449-452delCTGA is a common mutation in Japanese patients with MCADD.

PMID 23430840 2011 Relevance of expanded neonatal screening of medium-chain acyl co-a dehydrogenase deficiency: outcome of a decade in galicia (Spain).

PMID 21228398 2011 Carrier testing for severe childhood recessive diseases by next-generation sequencing.

PMID 27856190 2016 Screening of MCAD deficiency in Japan: 16years' experience of enzymatic and genetic evaluation.

PMID 27477829 2016 221 newborn-screened neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency: Findings from the Inborn Errors of Metabolism Collaborative.

PMID 27751224 2016 [An analysis of clinical characteristics and gene mutation in two patients with medium- and short-chain acyl-CoA dehydrogenase deficiency].

PMID 23700290 2013 Fatty Acid oxidation disorders in a chinese population in taiwan.

PMID 25087612 2014 Pathogenic variants for Mendelian and complex traits in exomes of 6,517 European and African Americans: implications for the return of incidental results.

PMID 8198141 1994 Most patients with MCAD deficiency are homozygous for a single disease-causing mutation (G985), causing a change from lysine to glutamate at position 304 (K304E) in the mature MCAD.

PMID 26223887 2015 Medium-chain acyl-CoA dehydrogenase deficiency associated with a novel splice mutation in the ACADM gene missed by newborn screening.

PMID 24799540 2014 The newborn screen was suggestive for MCAD deficiency, a diagnosis that was confirmed on genetic analysis that showed homozygosity for the disease-associated missense A985G mutation in the ACADM gene.

PMID 7929823 1994 Four compound heterozygote individuals from two unrelated families with A985G on one allele and a novel G to A mutation at nucleotide 583 (G583A) as the second mutant allele presented with MCAD deficiency in the first week of life.

PMID 8104486 1993 The influence of co-overexpression of the bacterial chaperonins GroEL and GroES on solubility, tetramer formation and enzyme activity of three variants of heterologously-expressed human medium-chain acyl-CoA dehydrogenase (MCAD) was analysed in order to investigate the molecular mechanism underlying MCAD deficiency caused by the prevalent K304E mutation.

PMID 2394825 1990 Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation.

PMID 7652482 1995 Molecular diagnosis and characterization of medium-chain acyl-CoA dehydrogenase deficiency.

PMID 24998633 2014 Synthesis framework estimating prevalence of MCADD and sensitivity of newborn screening programme in the absence of direct evidence.

PMID 24082139 2013 Personalized genomic disease risk of volunteers.

PMID 7904584 1994 Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: the prevalent mutation G985 (K304E) is subject to a strong founder effect from northwestern Europe.

PMID 25763512 2015 Abnormal Newborn Screening in a Healthy Infant of a Mother with Undiagnosed Medium-Chain Acyl-CoA Dehydrogenase Deficiency.

PMID 23842438 2013 Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency.

PMID 25333063 2014 Selected reaction monitoring as an effective method for reliable quantification of disease-associated proteins in maple syrup urine disease.

PMID 11349232 2001 High 985A-->G carrier frequencies in populations of European descent and the usual avoidance of recurrent disease episodes by patients diagnosed with MCAD deficiency who comply with a simple dietary treatment suggest that MCAD deficiency is a candidate in prospective screening of newborns.

PMID 20333879 2009 Hypoketotic hypoglycemia with myolysis and hypoparathyroidism: an unusual association in medium chain acyl-CoA desydrogenase deficiency (MCADD).

PMID 23574375 2014 Regional differences in the frequency of the c.985A>G ACADM mutation: findings from a meta-regression of genotyping and screening studies.

PMID 26215884 2015 Child Neurology: medium-chain acyl-coenzyme A dehydrogenase deficiency.

PMID 16737882 2006 The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome.

PMID 9797589 1998 Four groups were studied: (1) 35 children, aged 4 days to 16.2 years, with proven MCAD deficiency (mostly homozygous for the A985G mutation, none receiving carnitine supplements); (2) 2168 control children; (3) 482 neonates; and (4) 15 MCAD heterozygotes.

PMID 16763904 2007 In mass-screened newborn populations, the 985A>G (K329E) mutation accounts for 54-90% of disease alleles, with homozygotes representing about 47-80% of MCAD deficiency cases.

PMID 15915086 2005 We report the identification of the first Korean patient with MCAD deficiency, caused by a novel missense mutation in ACADM, 843A>T (R281S), and a 4-bp deletion, c.449_452delCTGA.

PMID 22796001 2012 Clinical and molecular aspects of Japanese children with medium chain acyl-CoA dehydrogenase deficiency.

PMID 23095120 2012 Sudden unexpected infant death (SUDI) in a newborn due to medium chain acyl CoA dehydrogenase (MCAD) deficiency with an unusual severe genotype.

PMID 18767270 2008 Newborn screening for MCAD deficiency: experience of the first three years in British Columbia, Canada.

PMID 25503862 2015 First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China.

PMID 15915086 2005 Genotypic differences of MCAD deficiency in the Asian population: novel genotype and clinical symptoms preceding newborn screening notification.

PMID 20567907 2010 Medium-chain acyl-CoA dehydrogenase deficiency in Saudi Arabia: incidence, genotype, and preventive implications.

rs1146586 in ACADM gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.