Mitochondrial fatty acid oxidation defects--remaining challenges

Niels Gregersen, Brage S Andresen, Christina B Pedersen, Rikke K J Olsen, Thomas J Corydon, Peter Bross

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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 approximately 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 Q(10). 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.

OriginalsprogEngelsk
TidsskriftJournal of Inherited Metabolic Disease
Vol/bind31
Udgave nummer5
Sider (fra-til)643-57
Antal sider15
ISSN0141-8955
DOI
StatusUdgivet - 2008

Fingeraftryk

Fatty Acids
Flavin-Adenine Dinucleotide
Publications
Oxidoreductases
Newborn Infant
Research
Coenzyme Q10 Deficiency

Citer dette

Gregersen, Niels ; Andresen, Brage S ; Pedersen, Christina B ; Olsen, Rikke K J ; Corydon, Thomas J ; Bross, Peter. / Mitochondrial fatty acid oxidation defects--remaining challenges. I: Journal of Inherited Metabolic Disease. 2008 ; Bind 31, Nr. 5. s. 643-57.
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abstract = "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 approximately 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 Q(10). 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.",
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Mitochondrial fatty acid oxidation defects--remaining challenges. / Gregersen, Niels; Andresen, Brage S; Pedersen, Christina B; Olsen, Rikke K J; Corydon, Thomas J; Bross, Peter.

I: Journal of Inherited Metabolic Disease, Bind 31, Nr. 5, 2008, s. 643-57.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Mitochondrial fatty acid oxidation defects--remaining challenges

AU - Gregersen, Niels

AU - Andresen, Brage S

AU - Pedersen, Christina B

AU - Olsen, Rikke K J

AU - Corydon, Thomas J

AU - Bross, Peter

PY - 2008

Y1 - 2008

N2 - 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 approximately 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 Q(10). 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.

AB - 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 approximately 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 Q(10). 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.

KW - Acyl-CoA Dehydrogenase

KW - Butyryl-CoA Dehydrogenase

KW - Fatty Acids

KW - Humans

KW - Metabolism, Inborn Errors

KW - Mitochondrial Diseases

KW - Models, Biological

KW - Multiple Acyl Coenzyme A Dehydrogenase Deficiency

KW - Mutation, Missense

KW - Oxidation-Reduction

KW - Protein Folding

U2 - 10.1007/s10545-008-0990-y

DO - 10.1007/s10545-008-0990-y

M3 - Journal article

C2 - 18836889

VL - 31

SP - 643

EP - 657

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 5

ER -