Acyl-CoA dehydrogenase 9 (ACAD 9) is the long-chain acyl-CoA dehydrogenase in human embryonic and fetal brain.
We recently reported the expression and activity of several fatty acid oxidation enzymes in human embryonic and fetal tissues including brain and spinal cord. Liver and heart showed expression of both very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) mRNA. However, while mRNA expression of LCHAD could be clearly detected in the retina and spinal cord, expression of VLCAD mRNA was low to undetectable in these tissues. Nevertheless, abundant acyl-CoA dehydrogenase (ACAD) activity was detected with palmitoyl-CoA as substrate in fetal central nervous tissue. These conflicting data suggested the presence of a different long-chain ACAD in human embryonic and fetal brain. In this study, using in situ hybridization as well as enzymatic studies, we identified acyl-CoA dehydrogenase 9 (ACAD 9) as the long-chain ACAD in human embryonic and fetal central nervous tissue. Until now, no clinical signs and symptoms of central nervous system involvement have been reported in VLCAD deficiency. A novel long-chain FAO defect, i.e., ACAD 9 deficiency with only central nervous system involvement, could, if not lethal during intra uterine development, easily escape proper diagnosis, since probably no classical signs and symptoms of FAO deficiency will be observed. Screening for ACAD 9 deficiency in patients with undefined neurological symptoms and/or impairment in neurological development of unknown origin is necessary to establish if ACAD 9 deficiency exists as a separate disease entity.
Oey
N A
NA
Department of Paediatrics, Laboratory for Genetic Metabolic Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ruiter
J P N
JP
Ijlst
L
L
Attie-Bitach
T
T
Vekemans
M
M
Wanders
R J A
RJ
Wijburg
F A
FA
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D044942:Acyl-CoA Dehydrogenase, Long-Chain / Q000172:deficiency / Q000378:metabolism*; D001921:Brain / Q000196:embryology / Q000201:enzymology*; D005333:Fetus / Q000201:enzymology; D006801:Humans; D017403:In Situ Hybridization
D015094:3-Hydroxyacyl CoA Dehydrogenases; D044942:Acyl-CoA Dehydrogenase, Long-Chain; C467805:ACADVL protein, human