PMID- 27943070
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 2192-8304 (Print)
IS  - 2192-8312 (Electronic)
IS  - 2192-8304 (Linking)
VI  - 35
DP  - 2017
TI  - Development of a Tandem Mass Spectrometry Method for Rapid Measurement of Medium- 
      and Very-Long-Chain Acyl-CoA Dehydrogenase Activity in Fibroblasts.
PG  - 71-78
LID - 10.1007/8904_2016_22 [doi]
AB  - Mitochondrial fatty acid oxidation is a vital biochemical process for energy 
      metabolism. Among the known fatty-acid metabolism disorders, very-long-chain 
      acyl-CoA dehydrogenase (VLCAD) deficiency and medium-chain acyl-CoA dehydrogenase 
      (MCAD) deficiency count among the most frequent. Both are potentially very 
      serious diseases as they carry a risk of severe neurological post-crisis 
      sequelae, and even sudden death. Diagnosis relies on plasma acylcarnitine profile 
      analysis and urine organic acid analysis, followed by genetic testing to confirm 
      diagnosis. However, in some cases, it is crucial to run a specific diagnostic 
      assay for enzyme activity, which is generally performed in leukocytes or 
      fibroblasts. The aim of this study was to address this need, first by developing 
      a MCAD and VLCAD enzyme activity-specific diagnostic assay in fibroblasts (by 
      measuring the reaction products, i.e. enoyl-CoA) via a rapid LC-MS/MS-based 
      technique, and then by testing MCAD-deficient patients (n = 6), VLCAD-deficient 
      patients (n = 10), and control patients (n = 12). MCAD activity was significantly 
      different in the MCAD-deficiency (MCADD) group (mean = 0.07 nmol C8:1 
      formed/min/mg protein) compared to the control group (mean = 0.36 nmol C8:1 
      formed/min/mg protein). All MCADD patients showed less than 35% residual MCAD 
      activity. VLCAD activity was significantly decreased in the VLCADD group 
      (mean = 0.06 nmol C16:1 formed/min/mg protein) compared to the control group 
      (mean = 0.86 nmol C16:1 formed/min/mg protein, respectively). All VLCADD patients 
      showed less than 35% residual VLCAD activity. This technique allowed also to 
      confirm that a novel ACADVL gene mutation (c.1400T>C) is responsible for a 
      defective VLCAD activity (residual activity at 10%).
FAU - Bouvier, Damien
AU  - Bouvier D
AD  - Service de Biochimie Medicale, Centre de Biologie, CHU Gabriel-Montpied, rue 
      Montalembert, 63000, Clermont-Ferrand, France.
AD  - Retinoids, Reproduction Developmental Diseases, School of Medicine, Clermont 
      Universite, Universite d'Auvergne, EA7281, 63000, Clermont-Ferrand, France.
FAU - Vianey-Saban, Christine
AU  - Vianey-Saban C
AD  - Service Maladies Hereditaires du Metabolisme et Depistage Neonatal, Centre de 
      Biologie et de Pathologie Est, CHU Lyon, INSERM U1060 CarMeN, 69500, Bron, 
      France.
FAU - Ruet, Severine
AU  - Ruet S
AD  - Service Maladies Hereditaires du Metabolisme et Depistage Neonatal, Centre de 
      Biologie et de Pathologie Est, CHU Lyon, INSERM U1060 CarMeN, 69500, Bron, 
      France.
FAU - Acquaviva, Cecile
AU  - Acquaviva C
AD  - Service Maladies Hereditaires du Metabolisme et Depistage Neonatal, Centre de 
      Biologie et de Pathologie Est, CHU Lyon, UMR 5305 CNRS/UCBL, 69500, Bron, France. 
      cecile.acquaviva-bourdain@chu-lyon.fr.
LA  - eng
PT  - Journal Article
DEP - 20161210
PL  - United States
TA  - JIMD Rep
JT  - JIMD reports
JID - 101568557
PMC - PMC5585096
EDAT- 2016/12/13 06:00
MHDA- 2016/12/13 06:01
PMCR- 2016/12/10
CRDT- 2016/12/13 06:00
PHST- 2016/07/19 00:00 [received]
PHST- 2016/11/09 00:00 [accepted]
PHST- 2016/11/07 00:00 [revised]
PHST- 2016/12/13 06:00 [pubmed]
PHST- 2016/12/13 06:01 [medline]
PHST- 2016/12/13 06:00 [entrez]
PHST- 2016/12/10 00:00 [pmc-release]
AID - 22 [pii]
AID - 10.1007/8904_2016_22 [doi]
PST - ppublish
SO  - JIMD Rep. 2017;35:71-78. doi: 10.1007/8904_2016_22. Epub 2016 Dec 10.