An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD)
Long-chain 3-hydroxyacyl-CoA deficiency (LCHADD) and mitochondrial trifunctional protein (MTPD) belong to a group of inherited metabolic diseases affecting the degradation of long-chain chain fatty acids. During metabolic decompensation the incomplete degradation of fatty acids results in life-threa...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/13/7144 |
| _version_ | 1797479735239901184 |
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| author | Sara Tucci |
| author_facet | Sara Tucci |
| author_sort | Sara Tucci |
| collection | DOAJ |
| description | Long-chain 3-hydroxyacyl-CoA deficiency (LCHADD) and mitochondrial trifunctional protein (MTPD) belong to a group of inherited metabolic diseases affecting the degradation of long-chain chain fatty acids. During metabolic decompensation the incomplete degradation of fatty acids results in life-threatening episodes, coma and death. Despite fast identification at neonatal screening, LCHADD/MTPD present with progressive neurodegenerative symptoms originally attributed to the accumulation of toxic hydroxyl acylcarnitines and energy deficiency. Recently, it has been shown that LCHADD human fibroblasts display a disease-specific alteration of complex lipids. Accumulating fatty acids, due to defective β-oxidation, contribute to a remodeling of several lipid classes including mitochondrial cardiolipins and sphingolipids. In the last years the face of LCHADD/MTPD has changed. The reported dysregulation of complex lipids other than the simple acylcarnitines represents a novel aspect of disease development. Indeed, aberrant lipid profiles have already been associated with other neurodegenerative diseases such as Parkinson’s Disease, Alzheimer’s Disease, amyotrophic lateral sclerosis and retinopathy. Today, the physiopathology that underlies the development of the progressive neuropathic symptoms in LCHADD/MTPD is not fully understood. Here, we hypothesize an alternative disease-causing mechanism that contemplates the interaction of several factors that acting in concert contribute to the heterogeneous clinical phenotype. |
| first_indexed | 2024-03-09T21:50:04Z |
| format | Article |
| id | doaj.art-9d862594fab24e2b8dd59873e20ebb73 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:50:04Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9d862594fab24e2b8dd59873e20ebb732023-11-23T20:08:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313714410.3390/ijms23137144An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD)Sara Tucci0Pharmacy, Medical Center, University of Freiburg, 79106 Freiburg, GermanyLong-chain 3-hydroxyacyl-CoA deficiency (LCHADD) and mitochondrial trifunctional protein (MTPD) belong to a group of inherited metabolic diseases affecting the degradation of long-chain chain fatty acids. During metabolic decompensation the incomplete degradation of fatty acids results in life-threatening episodes, coma and death. Despite fast identification at neonatal screening, LCHADD/MTPD present with progressive neurodegenerative symptoms originally attributed to the accumulation of toxic hydroxyl acylcarnitines and energy deficiency. Recently, it has been shown that LCHADD human fibroblasts display a disease-specific alteration of complex lipids. Accumulating fatty acids, due to defective β-oxidation, contribute to a remodeling of several lipid classes including mitochondrial cardiolipins and sphingolipids. In the last years the face of LCHADD/MTPD has changed. The reported dysregulation of complex lipids other than the simple acylcarnitines represents a novel aspect of disease development. Indeed, aberrant lipid profiles have already been associated with other neurodegenerative diseases such as Parkinson’s Disease, Alzheimer’s Disease, amyotrophic lateral sclerosis and retinopathy. Today, the physiopathology that underlies the development of the progressive neuropathic symptoms in LCHADD/MTPD is not fully understood. Here, we hypothesize an alternative disease-causing mechanism that contemplates the interaction of several factors that acting in concert contribute to the heterogeneous clinical phenotype.https://www.mdpi.com/1422-0067/23/13/7144long-chain fatty acid oxidation disordersLCHADDlipidomicssphyngomyelines and ceramidesneurodegeneration |
| spellingShingle | Sara Tucci An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD) International Journal of Molecular Sciences long-chain fatty acid oxidation disorders LCHADD lipidomics sphyngomyelines and ceramides neurodegeneration |
| title | An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD) |
| title_full | An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD) |
| title_fullStr | An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD) |
| title_full_unstemmed | An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD) |
| title_short | An Altered Sphingolipid Profile as a Risk Factor for Progressive Neurodegeneration in Long-Chain 3-Hydroxyacyl-CoA Deficiency (LCHADD) |
| title_sort | altered sphingolipid profile as a risk factor for progressive neurodegeneration in long chain 3 hydroxyacyl coa deficiency lchadd |
| topic | long-chain fatty acid oxidation disorders LCHADD lipidomics sphyngomyelines and ceramides neurodegeneration |
| url | https://www.mdpi.com/1422-0067/23/13/7144 |
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