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Development of a Tandem Mass Spectrometry Method for Rapid Measurement of Medium- and Very-Long-Chain Acyl-CoA Dehydrogenase Activity in Fibroblasts.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bouvier, Damien Vianey-Saban, Christine Ruet, Séverine Acquaviva, Cécile |
| Copyright Year | 2016 |
| Abstract | 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%). |
| Starting Page | 71 |
| Ending Page | 78 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://pdf.xuebalib.com/xuebalib.com.30893.pdf |
| PubMed reference number | 27943070v1 |
| Alternate Webpage(s) | https://doi.org/10.1007/8904_2016_22 |
| DOI | 10.1007/8904_2016_22 |
| Journal | JIMD reports |
| Volume Number | 35 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acyl Coenzyme A Biochemical Processes Control Groups Deficiency of butyryl-CoA dehydrogenase Energy Metabolism Fatty Acids Gene Mutation Genetic screening method Lesch-Nyhan Syndrome Nanomole Organic acid (substance) Patients Sequela of disorder Sudden death Tandem Mass Spectrometry Very long chain acyl-CoA dehydrogenase deficiency acylcarnitine fatty acid oxidation |
| Content Type | Text |
| Resource Type | Article |
