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Mitochondrial fatty acid oxidation defects—remaining challenges

  • Niels Gregersen
  • Brage S. Andresen
  • Christina B. Pedersen
  • Rikke K. J. Olsen
  • Thomas J. Corydon
  • Peter Bross
Komrower Lecture

Summary

Mitochondrial fatty acid oxidation defects have been recognized since the early 1970s. The discovery rate has been rather constant, with 3–4 ‘new’ disorders identified every decade and with the most recent example, ACAD9 deficiency, reported in 2007. In this presentation we will focus on three of the ‘old’ defects: medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, riboflavin responsive multiple acyl-CoA dehydrogenation (RR-MAD) deficiency, and short-chain acyl-CoA dehydrogenase (SCAD) deficiency. These disorders have been discussed in many publications and at countless conference presentations, and many questions relating to them have been answered. However, continuing clinical and pathophysiological research has raised many further questions, and new ideas and methodologies may be required to answer these. We will discuss these challenges. For MCAD deficiency the key question is why 80% of symptomatic patients are homozygous for the prevalent ACADM gene variation c.985A > G whereas this is found in only ∼50% of newborns with a positive screen. For RR-MAD deficiency, the challenge is to find the connection between variations in the ETFDH gene and the observed deficiency of a number of different mitochondrial dehydrogenases as well as deficiency of FAD and coenzyme Q10. With SCAD deficiency, the challenge is to elucidate whether ACADS gene variations are disease-associated, especially when combined with other genetic/cellular/environmental factors, which may act synergistically.

Keywords

Carnitine Missense Variation Glutaric Aciduria Type Electron Transfer Flavoprotein Dicarboxylic Aciduria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Niels Gregersen
    • 1
    • 3
  • Brage S. Andresen
    • 1
    • 2
  • Christina B. Pedersen
    • 1
  • Rikke K. J. Olsen
    • 1
  • Thomas J. Corydon
    • 2
  • Peter Bross
    • 1
  1. 1.Research Unit for Molecular Medicine, Institute of Clinical Medicine, The Faculty of Health SciencesAarhus UniversityAarhus NDenmark
  2. 2.Institute of Human Genetics, The Faculty of Health SciencesAarhus UniversityAarhus CDenmark
  3. 3.Research Unit for Molecular Medicine, Institute of Clinical MedicineAarhus University, Aarhus University HospitalAarhus NDenmark

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