Elsevier

Clinica Chimica Acta

Volume 203, Issue 1, 9 November 1991, Pages 23-34
Clinica Chimica Acta

Specific diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in dried blood spots by a polymerase chain reaction (PCR) assay detecting a point-mutation (G985) in the MCAD gene

https://doi.org/10.1016/0009-8981(91)90153-4Get rights and content

Abstract

The discovery of a point-mutation, adenine-to-guanine, at position 985 in the gene coding for MCAD (G985), gave the basis for an easy and specific polymerase chain reaction test. We tested the specificity of such a PCR based assay and detected correctly G985 and A985 in sequence verified cDNA clones. We showed that the G985 mutation is present in genomic DNA from 48 of 50 patients with confirmed MCAD deficiency, originating from various European countries, Australia and the USA. On the basis of this high frequency of the G985 mutation among patients, we improved and optimized the assay with respect to reliability and convenience for routine diagnostic and screening purposes. As little as 2 μl blood from filter-paper blood-spots (Guthrie spots) is sufficient for the test.

References (22)

  • JWT Seakins et al.

    The use of phenylpropionic acid as a loading test for medium-chain acyl-CoA dehydrogenase deficiency

    J Inher Metab Dis

    (1988)
  • Cited by (78)

    • Analysis of gene mutations of medium-chain acyl-coenzyme a dehydrogenase deficiency (MCADD) by next-generation sequencing in Henan, China

      2022, Clinica Chimica Acta
      Citation Excerpt :

      The incidence, the spectrum, and the genetic characteristics of hypermethioninemia vary dramatically in different regions and populations. ACADM pathogenic variant c.985A > G (p.Lys329Glu) is the most common pathogenic variant in European populations[10]. Individuals with homozygous variant for the common c.985A > G have the highest C8 newborn screen values and are most likely to have neonatal symptoms[10,11].

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

      2012, Clinical Biochemistry
      Citation Excerpt :

      Real time PCR-based genotyping assays have been designed for the rapid detection of the aforementioned mutations, in order to further assess in a future study the prevalence of this frameshift aberration in the Greek population. As far as the c.985A > G allele in our confirmed MCADD cohort is concerned, the frequency of heterozygote samples identified through NBS is much less than the one detected in the clinically ascertained cohort, which is in concordance with the literature [12]. The higher genotypic heterogeneity of the NBS group is also highlighted by the identification of a novel possibly pathogenic allele.

    • Clinical and molecular aspects of Japanese children with medium chain acyl-CoA dehydrogenase deficiency

      2012, Molecular Genetics and Metabolism
      Citation Excerpt :

      Blood acylcarnitine, urinary organic acid analyses, MCAD activity and mutation analyses are major tools for diagnosis of MCADD. A common c.985A > G mutation has been reported in 80–90% of Caucasian patients [8–16] while c.449–452delCTGA mutation was identified in 45% of mutant alleles in Japanese patients with MCADD [17]. In recent years, the detection incidence of the presymptomatic patients with MCADD has increased since the neonatal mass screening was expanded in Japan.

    • Genotypic differences of MCAD deficiency in the Asian population: Novel genotype and clinical symptoms preceding newborn screening notification

      2005, Genetics in Medicine
      Citation Excerpt :

      The gene for MCAD, ACADM, is located on chromosome 1p31 and consists of 12 exons spanning 44 kb of DNA.8 The 985A>G (p.K329E) mutation is the most common gene variant accounting for 85% to 90% of alleles detected in clinically symptomatic Caucasian patients of Northern European descent but only for 60% of defective alleles of patients diagnosed by NBS.3,9,10. In addition, approximately 40 other, mostly private mutations have been reported.3,4,11

    View all citing articles on Scopus
    View full text