Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases
Even though the application of Next-Generation Sequencing (NGS) has significantly facilitated the identification of disease-associated mutations, the diagnostic rate of rare diseases is still below 50%. This causes a diagnostic odyssey and prevents specific treatment, as well as genetic counseling f...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1709 |
| _version_ | 1797441090754707456 |
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| author | Martina Zandl-Lang Barbara Plecko Harald Köfeler |
| author_facet | Martina Zandl-Lang Barbara Plecko Harald Köfeler |
| author_sort | Martina Zandl-Lang |
| collection | DOAJ |
| description | Even though the application of Next-Generation Sequencing (NGS) has significantly facilitated the identification of disease-associated mutations, the diagnostic rate of rare diseases is still below 50%. This causes a diagnostic odyssey and prevents specific treatment, as well as genetic counseling for further family planning. Increasing the diagnostic rate and reducing the time to diagnosis in children with unclear disease are crucial for a better patient outcome and improvement of quality of life. In many cases, NGS reveals variants of unknown significance (VUS) that need further investigations. The delineation of novel (lipid) biomarkers is not only crucial to prove the pathogenicity of VUS, but provides surrogate parameters for the monitoring of disease progression and therapeutic interventions. Lipids are essential organic compounds in living organisms, serving as building blocks for cellular membranes, energy storage and signaling molecules. Among other disorders, an imbalance in lipid homeostasis can lead to chronic inflammation, vascular dysfunction and neurodegenerative diseases. Therefore, analyzing lipids in biological samples provides great insight into the underlying functional role of lipids in healthy and disease statuses. The method of choice for lipid analysis and/or huge assemblies of lipids (=lipidome) is mass spectrometry due to its high sensitivity and specificity. Due to the inherent chemical complexity of the lipidome and the consequent challenges associated with analyzing it, progress in the field of lipidomics has lagged behind other omics disciplines. However, compared to the previous decade, the output of publications on lipidomics has increased more than 17-fold within the last decade and has, therefore, become one of the fastest-growing research fields. Combining multiple omics approaches will provide a unique and efficient tool for determining pathogenicity of VUS at the functional level, and thereby identifying rare, as well as novel, genetic disorders by molecular techniques and biochemical analyses. |
| first_indexed | 2024-03-09T12:18:02Z |
| format | Article |
| id | doaj.art-859315a5d7c94b76b5ec44e9299e825c |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:18:02Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-859315a5d7c94b76b5ec44e9299e825c2023-11-30T22:44:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242170910.3390/ijms24021709Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic DiseasesMartina Zandl-Lang0Barbara Plecko1Harald Köfeler2Division of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, AustriaDivision of General Pediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Graz, 8036 Graz, AustriaCore Facility Mass Spectrometry, ZMF, Medical University of Graz, 8036 Graz, AustriaEven though the application of Next-Generation Sequencing (NGS) has significantly facilitated the identification of disease-associated mutations, the diagnostic rate of rare diseases is still below 50%. This causes a diagnostic odyssey and prevents specific treatment, as well as genetic counseling for further family planning. Increasing the diagnostic rate and reducing the time to diagnosis in children with unclear disease are crucial for a better patient outcome and improvement of quality of life. In many cases, NGS reveals variants of unknown significance (VUS) that need further investigations. The delineation of novel (lipid) biomarkers is not only crucial to prove the pathogenicity of VUS, but provides surrogate parameters for the monitoring of disease progression and therapeutic interventions. Lipids are essential organic compounds in living organisms, serving as building blocks for cellular membranes, energy storage and signaling molecules. Among other disorders, an imbalance in lipid homeostasis can lead to chronic inflammation, vascular dysfunction and neurodegenerative diseases. Therefore, analyzing lipids in biological samples provides great insight into the underlying functional role of lipids in healthy and disease statuses. The method of choice for lipid analysis and/or huge assemblies of lipids (=lipidome) is mass spectrometry due to its high sensitivity and specificity. Due to the inherent chemical complexity of the lipidome and the consequent challenges associated with analyzing it, progress in the field of lipidomics has lagged behind other omics disciplines. However, compared to the previous decade, the output of publications on lipidomics has increased more than 17-fold within the last decade and has, therefore, become one of the fastest-growing research fields. Combining multiple omics approaches will provide a unique and efficient tool for determining pathogenicity of VUS at the functional level, and thereby identifying rare, as well as novel, genetic disorders by molecular techniques and biochemical analyses.https://www.mdpi.com/1422-0067/24/2/1709lipidomicsmass spectrometryrare diseasesorphan diseases |
| spellingShingle | Martina Zandl-Lang Barbara Plecko Harald Köfeler Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases International Journal of Molecular Sciences lipidomics mass spectrometry rare diseases orphan diseases |
| title | Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases |
| title_full | Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases |
| title_fullStr | Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases |
| title_full_unstemmed | Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases |
| title_short | Lipidomics—Paving the Road towards Better Insight and Precision Medicine in Rare Metabolic Diseases |
| title_sort | lipidomics paving the road towards better insight and precision medicine in rare metabolic diseases |
| topic | lipidomics mass spectrometry rare diseases orphan diseases |
| url | https://www.mdpi.com/1422-0067/24/2/1709 |
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