Jager, E. (Emmalie) (2017) Promise of predictive biomarkers for disease severity in Medium-Chain Acyl-CoA Dehydrogenase Deficiency. thesis, Medicine.
Full text available on request.Abstract
BACKGROUND- Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) is the most common inheritable disorder of mitochondrial fatty acid oxidation (mFAO). It has been suggested that many MCADD patients currently detected by the neonatal bloodspot screening may remain completely asymptomatic, despite of treatment. To avoid unnecessary treatment novel strategies for risk stratification in MCADD are needed. In this study a multi-omics approach was used to in vitro identify potential biomarkers for risk stratification in MCADD. METHODS- Quantitative targeted metabolomic and proteomic data of skin fibroblast of genetically homogenous (ACADM c.985A>C homozygote) symptomatic symptomatic (n=4) and asymptomatic (n=6) MCADD patients were generated. Data were compared between symptomatic and asymptomatic MCADD, patients with an alternative mitochondrial fatty acid oxidation (n=4) defect and healthy controls (n=6). The potential as predictive biomarkers were tested for by principal component analysis, as well as discriminant function analysis. RESULT- Intracellular accumulation of acyl-carnitines was observed in patients with a mitochondrial fatty acid oxidation disorder and markedly elevated intracellular C3 and C6 in asymptomatic MCADD patients. The higher mitochondrial SOD2 expression was the most prominent of several differences in mitochondrial protein expression between symptomatic and asymptomatic MCADD patients. CONCLUSION- This study is the first to identify differences in biochemical profiles between genetically homogenous symptomatic and asymptomatic MCADD patients, thereby generating great promise for finding suitable biomarkers for risk stratification in MCADD and may pave the way for better and more personalized treatment of mFAO disorder patients.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervised by: and Bakker, Prof. Dr. Barbara M. and Derks, Dr. Terry. G.J. MD and Martines, Drs. ir. A.M.F and Department of Pediatrics, University Medical Center Groninge |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:06 |
| Last Modified: | 25 Jun 2020 11:06 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2575 |
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