The authors report no conflict of interests.
Retrospective study of the medium-chain acyl-CoA dehydrogenase deficiency in Portugal
Article first published online: 28 JUL 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 85, Issue 6, pages 555–561, June 2014
How to Cite
Ventura, F.V., Leandro, P., Luz, A., Rivera, I.A., Silva, M.F.B., Ramos, R., Rocha, H., Lopes, A., Fonseca, H., Gaspar, A., Diogo, L., Martins, E., Leão-Teles, E., Vilarinho, L. and Tavares de Almeida, I. (2014), Retrospective study of the medium-chain acyl-CoA dehydrogenase deficiency in Portugal. Clinical Genetics, 85: 555–561. doi: 10.1111/cge.12227
These two authors contributed equivalently to this work.
- Issue published online: 26 APR 2014
- Article first published online: 28 JUL 2013
- Accepted manuscript online: 6 JUL 2013 08:48AM EST
- Manuscript Revised: 2 JUL 2013
- Manuscript Accepted: 2 JUL 2013
- Manuscript Received: 24 APR 2013
- Portuguese Society for Metabolic Disorders
- Fundação para a Ciência e Tecnologia
- inborn errors of metabolism;
- mitochondrial fatty acid β-oxidation disorders;
- newborn screening
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the commonest genetic defect of mitochondrial fatty acid β-oxidation. About 60% of MCADD patients are homozygous for the c.985A>G (p.Lys329Glu) mutation in the ACADM gene (G985 allele). Herein, we present the first report on the molecular and biochemical spectrum of Portuguese MCADD population. From the 109 patients studied, 83 were diagnosed after inclusion of MCADD in the national newborn screening, 8 following the onset of symptoms and 18 through segregation studies. Gypsy ancestry was identified in 85/109 patients. The G985 allele was found in homozygosity in 102/109 patients, in compound heterozygosity in 6/109 and was absent in one patient. Segregation studies in the Gypsy families showed that 93/123 relatives were carriers of the G985 allele, suggesting its high prevalence in this ethnic group. Additionally, three new substitutions—c.218A>G (p.Tyr73Cys), c.503A>T (p.Asp168Val) and c.1205G>T (p.Gly402Val)—were identified. Despite the particularity of the MCADD population investigated, the G985 allele was found in linkage disequilibrium with H1(112) haplotype. Furthermore, two novel haplotypes, H5(212) and H6(122) were revealed.