Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare, life-threatening condition. Early diagnosis by screening asymptomatic newborns may improve outcome, but the benefit to newborns identified with variants not encountered clinically is uncertain

Andresen, BS

Besley, G

Dalton, RN

Dezateux, C

Downing, M

Green, A

Henderson, M

Khalid, JM

Krywawych, S

Leonard, J

Oerton, J

PubMed

Background Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is a rare, life-threatening condition. Early diagnosis by screening asymptomatic newborns may improve outcome, but the benefit to newborns identified with variants not encountered clinically is uncertain. Objective To estimate, overall and by ethnic group: screen-positive prevalence and predictive value (PPV); MCADD prevalence; proportion MCADD variants detected of predicted definite or uncertain clinical importance. Setting All births in areas of high ethnic minority prevalence in England. Methods Prospective multicentre pilot screening service; testing at age five to eight days; standardized screening, diagnostic and management protocols; independent expert review of screen-positive cases to assign MCADD diagnosis and predicted clinical importance (definite or uncertain). Results Approximately 1.5 million babies (79% white; 10% Asian) were screened. MCADD was confirmed in 147 of 190 babies with a positive screening result (screen-positive prevalence: 1.20 per 10,000; MCADD prevalence: 0.94 per 10,000; PPV 77% [95% CI 71–83]), comprising 103 (70%) with MCADD variants of definite clinical importance (95 white [95%]; 2 Asian [2%]) and 44 (30%) with variants of uncertain clinical importance (29 white [67%]; 12 Asian [28%]). Conclusion One baby in every 10,000 born in England is diagnosed with MCADD by newborn screening; around 60 babies each year. While the majority of MCADD variants detected are predicted to be of definite clinical importance, this varies according to ethnic group, with variants of uncertain importance most commonly found in Asian babies. These findings provide support for MCADD screening but highlight the need to take account of the ethnic diversity of the population tested at implementation. </jats:sec

Juliet Oerton

Javaria M Khalid

Guy Besley

R Neil Dalton

Melanie Downing

Anne Green

Mick Henderson

Steve Krywawych

James Leonard

Brage S Andresen

Carol Dezateux

Crossref

Journal of Medical Screening

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

: The UK Collaborative Study of Newborn Screening for MCADD was funded by a grant from the Department of Health (England) and commissioned by the UK National Screening Committee. This work was undertaken at GOSH/ UCL Institute of Child Health which received a proportion of funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme. The MRC Centre of Epidemiology for Child Health benefits from funding from the Medical Research Council (G0400546)

Queen Mary Research Online

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

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A method for quantitative acylcarnitine proﬁling in human skin ﬁbroblasts using unlabelled palmitic acid: diagnosis of fatty acid oxidation disorders and differentiation between biochemical phenotypes of MCAD deﬁciency.

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

Birthweight and gestational age by ethnic group,

Blood acylcarnitine levels in normal newborns and heterozygotes for medium-chain acyl-CoA dehydrogenase deﬁciency: a relationship between genotype and biochemical phenotype?

Detection of urinary hexanoylglycine in the diagnosis of MCAD deﬁciency from newborn screening.

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

Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress.

Electrospray tandem mass spectrometry for analysis of acylcarnitines in dried postmortem blood specimens collected at autopsy from infants with unexplained cause of death.

Ethnicity of children with homozygous c.985A.G medium-chain acyl-CoA dehydrogenase deﬁciency: ﬁndings from screening approximately 1.1 million newborn infants.

Evaluation of newborn screening for medium chain acyl-CoA dehydrogenase deﬁciency in 275000 babies. Arch Dis Child

Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.

Expanded newborn screening in Europe

Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics

Fatty acid oxidation disorders: outcome and long-term prognosis.

Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany.

Lack of genotype-phenotype correlations and outcome in MCAD deﬁciency diagnosed by newborn screening in

Medium chain acyl-CoA dehydrogenase deﬁciency caused by a deletion of exons 11 and 12. Hum Mol Genet

Medium chain acyl-CoA dehydrogenase deﬁciency. Arch Dis Child

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

Medium-chain acyl-coenzyme A dehydrogenase deﬁciency: clinical course in 120 affected children.

Mitochondrial fatty acid oxidation defects–remaining challenges.

Molecular and functional characterisation of mild MCAD deﬁciency. Hum Genet

Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deﬁciency.

Neonatal screening for inborn errors of metabolism: cost, yield and outcome. Health Technol Assess

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

Neonatal screening for medium-chain acyl-CoA dehydrogenase deﬁciency. Lancet

Newborn screening for disorders of fatty-acid oxidation: experience and recommendations from an expert meeting.

Newborn screening for inborn errors of metabolism: a systematic review. Health Technol Assess

Newborn screening for MCAD deﬁciency: acylcarnitine C8/C10 ratio at day 6 differentiates affected cases from carriers.

Newborn screening for medium chain acyl CoA dehydrogenase deﬁciency. Arch Dis Child

Newborn screening for medium-chain acyl-CoA dehydrogenase deﬁciency: a global perspective.

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.

Outcome of medium chain acyl-CoA dehydrogenase deﬁciency after diagnosis. Arch Dis Child

Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deﬁciency in Australia: a cohort study.

p22.2p31.1 and medium-chain acyl-CoA dehydrogenase deﬁciency in a patient with global developmental delay.

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

Prospective surveillance study of medium chain acyl-CoA dehydrogenase deﬁciency in the UK. Arch Dis Child

Quality Assuring a Multicentre Newborn Screening Programme for MCADD in the UK.

Rapid diagnosis of MCAD deﬁciency: quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry. Clin Chem

Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deﬁciency homozygous for c.985A.G identiﬁed by neonatal screening.

Relationship of octanoylcarnitine concentrations to age at sampling in unaffected newborns screened for medium-chain acyl-CoA dehydrogenase deﬁciency.

Screening Programme Centre. Standards and Guidelines for Newborn Blood Spot Screening.

Spectrum of medium-chain acyl-CoA dehydrogenase deﬁciency detected by newborn screening. Pediatrics

Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Clin Chem

The consequences of extended newborn screening programmes: Do we know who needs treatment?

The difference between observed and expected prevalence of MCAD deﬁciency in The Netherlands: a genetic epidemiological study.

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

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

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

The use of [9,10-3H]myristate, [9,10-3H]palmitate and [9,10-3H]oleate for the detection and diagnosis of medium and long-chain fatty acid oxidation disorders in intact cultured ﬁbroblasts. Adv Exp Med Biol

Twenty years of active paediatric surveillance in the the UK and Republic of Ireland.

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

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