Characterization of the molecular spectrum of Medium-Chain Acyl-CoA Dehydrogenase Deficiency in a Greek newborns cohort: Identification of a novel variant

• Published in: Clinical biochemistry Vol. 45; no. 15; pp. 1167 - 1172
• Main Authors: Thodi, Georgia, Georgiou, Vassiliki, Molou, Elina, Loukas, Yannis L., Dotsikas, Yannis, Biti, Sofia, Papadopoulos, Konstantinos, Doulgerakis, Emmanuel
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.10.2012; Elsevier
• Subjects: Acyl-CoA Dehydrogenase - deficiency; Acyl-CoA Dehydrogenase - genetics; Alleles; Base Sequence; Biological and medical sciences; Carnitine - analogs & derivatives; Carnitine - blood; Carnitine - urine; Disorders of blood lipids. Hyperlipoproteinemia; Errors of metabolism; GC/MS; Genetic Association Studies; Greece - epidemiology; Humans; Infant, Newborn; Investigative techniques, diagnostic techniques (general aspects); Lipids (lysosomal enzyme disorders, storage diseases); MCAD deficiency; Medical sciences; Metabolic diseases; Mitochondrial Diseases - epidemiology; Mitochondrial Diseases - genetics; Mitochondrial Diseases - urine; Molecular Sequence Data; Mutations; Neonatal Screening; Newborn screening; Polymorphism, Restriction Fragment Length; Prevalence; Sequence Analysis, DNA; Sequencing; Greece; Newborn screening; Mutations; MCAD deficiency; Sequencing; GC/MS; Genetic variability; Lipids; Enzymopathy; Cohort study; Clinical biology; Molecular epidemiology; Genetics; Human; Hypolipemia; Nucleotide sequence; Exploration; Metabolic diseases; Genotype; Medium chain; Medical screening; Genetic disease; Variant; Gas chromatography; Newborn; Acyl-CoA dehydrogenase deficiency; Mutation; Greek; Mass spectrometry
• ISSN: 0009-9120; 1873-2933
• DOI: 10.1016/j.clinbiochem.2012.05.030

The purpose of the current study was to screen newborns in Greece and to identify the responsible mutations for Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD). 47.812 neonates were screened for the potential presence of MCADD in Greece, via a LC–MS/MS protocol. The “suspected” samples were subjected to genetic testing via PCR–RFLP and sequencing of the coding region of the ACADM gene. Urine samples were collected and then analyzed with a GC/MS method. The MCADD prevalence is 1 in 15,937 births. The alleles c.985A>G and c.245insT were detected in the 29.2% and 20.8% of the “suspected” cohort, respectively. A novel variant with potential pathogenicity was identified. The c.245insT allele seems to prevail in the Greek cohort of “suspected” specimens. Therefore, this variant along with the c.985A>G allele could constitute a panel for both prenatal and neonatal MCADD screening in the Greek population. ► Determination of MCADD prevalence in the Greek population ► The predominant disease causing alleles have been revealed. ► The c.245insT allele, seems to prevail in the Greek cohort of “suspected” specimens. ► A novel variant with potential pathogenicity was also identified.