Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation
Abstract Background Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric probl...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-02-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13023-020-1329-5 |
| _version_ | 1828157476630953984 |
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| author | Claire Cannet Andrea Pilotto Júlio César Rocha Hartmut Schäfer Manfred Spraul Daniela Berg Peter Nawroth Christian Kasperk Gwendolyn Gramer Dorothea Haas David Piel Stefan Kölker Georg Hoffmann Peter Freisinger Friedrich Trefz |
| author_facet | Claire Cannet Andrea Pilotto Júlio César Rocha Hartmut Schäfer Manfred Spraul Daniela Berg Peter Nawroth Christian Kasperk Gwendolyn Gramer Dorothea Haas David Piel Stefan Kölker Georg Hoffmann Peter Freisinger Friedrich Trefz |
| author_sort | Claire Cannet |
| collection | DOAJ |
| description | Abstract Background Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric problems, microcephaly, motor deficits, eczematous rash, autism, seizures, and developmental problems. There is a controversial discussion of whether patients with PKU have an additional risk for atherosclerosis due to interference of Phe with cholesterol synthesis and LDL-cholesterol regulation. Since cholesterol also plays a role in membrane structure and myelination, better insight into the clinical significance of the impact of Phe on lipoprotein metabolism is desirable. In 22 treated PKU patients (mean age 38.7 years) and 14 healthy controls (mean age 35.2 years), we investigated plasma with NMR spectroscopy and quantified 105 lipoprotein parameters (including lipoprotein subclasses) and 24 low molecular weight parameters. Analysis was performed on a 600 MHz Bruker AVANCE IVDr spectrometer as previously described. Results Concurrent plasma Phe in PKU patients showed a wide range with a mean of 899 μmol/L (50–1318 μmol/L). Total cholesterol and LDL-cholesterol were significantly lower in PKU patients versus controls: 179.4 versus 200.9 mg/dL (p < 0.02) and 79.5 versus 104.1 mg/dL (p < 0.0038), respectively. PKU patients also had lower levels of 22 LDL subclasses with the greatest differences in LDL2 Apo-B, LDL2 Particle Number, LDL2-phospholipids, and LDL2-cholesterol (p < 0.0001). There was a slight negative correlation of total cholesterol and LDL-cholesterol with concurrent Phe level. VLDL5-free cholesterol, VLDL5-cholesterol, VLDL5-phospholipids, and VLDL4-free cholesterol showed a significant (p < 0.05) negative correlation with concurrent Phe level. There was no difference in HDL and their subclasses between PKU patients and controls. Tyrosine, glutamine, and creatinine were significantly lower in PKU patients compared to controls, while citric and glutamic acids were significantly higher. Conclusions Using NMR spectroscopy, a unique lipoprotein profile in PKU patients can be demonstrated which mimics a non-atherogenic profile as seen in patients treated by statins. |
| first_indexed | 2024-04-11T23:30:04Z |
| format | Article |
| id | doaj.art-8b6f46eb86264e03ba005cf5a9db5cf9 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-11T23:30:04Z |
| publishDate | 2020-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-8b6f46eb86264e03ba005cf5a9db5cf92022-12-22T03:57:11ZengBMCOrphanet Journal of Rare Diseases1750-11722020-02-011511710.1186/s13023-020-1329-5Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigationClaire Cannet0Andrea Pilotto1Júlio César Rocha2Hartmut Schäfer3Manfred Spraul4Daniela Berg5Peter Nawroth6Christian Kasperk7Gwendolyn Gramer8Dorothea Haas9David Piel10Stefan Kölker11Georg Hoffmann12Peter Freisinger13Friedrich Trefz14Bruker BioSpin GmbHDepartment of Neurodegeneration, Hertie Institute of Clinical Brain Research, University of TübingenCenter for Health Technology and Services Research (CINTESIS)Bruker BioSpin GmbHBruker BioSpin GmbHDepartment of Neurology, University-Hospital-Schleswig-Holstein, Christian-Albrechts-UniversityDepartment of Endocrinology and Metabolism, University HospitalDepartment of Endocrinology and Metabolism, University HospitalDepartment of Pediatrics, Centre for Pediatric and Adolescent Medicine, Division of Neuropaediatrics and Metabolic Medicine, University HospitalDepartment of Pediatrics, Centre for Pediatric and Adolescent Medicine, Division of Neuropaediatrics and Metabolic Medicine, University HospitalPediatrics, Reutlingen HospitalDepartment of Pediatrics, Centre for Pediatric and Adolescent Medicine, Division of Neuropaediatrics and Metabolic Medicine, University HospitalDepartment of Pediatrics, Centre for Pediatric and Adolescent Medicine, Division of Neuropaediatrics and Metabolic Medicine, University HospitalPediatrics, Reutlingen HospitalDepartment of Pediatrics, Centre for Pediatric and Adolescent Medicine, Division of Neuropaediatrics and Metabolic Medicine, University HospitalAbstract Background Phenylketonuria (PKU; OMIM#261600) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene resulting in high phenylalanine (Phe) in blood and brain. If not treated early this results in intellectual disability, behavioral and psychiatric problems, microcephaly, motor deficits, eczematous rash, autism, seizures, and developmental problems. There is a controversial discussion of whether patients with PKU have an additional risk for atherosclerosis due to interference of Phe with cholesterol synthesis and LDL-cholesterol regulation. Since cholesterol also plays a role in membrane structure and myelination, better insight into the clinical significance of the impact of Phe on lipoprotein metabolism is desirable. In 22 treated PKU patients (mean age 38.7 years) and 14 healthy controls (mean age 35.2 years), we investigated plasma with NMR spectroscopy and quantified 105 lipoprotein parameters (including lipoprotein subclasses) and 24 low molecular weight parameters. Analysis was performed on a 600 MHz Bruker AVANCE IVDr spectrometer as previously described. Results Concurrent plasma Phe in PKU patients showed a wide range with a mean of 899 μmol/L (50–1318 μmol/L). Total cholesterol and LDL-cholesterol were significantly lower in PKU patients versus controls: 179.4 versus 200.9 mg/dL (p < 0.02) and 79.5 versus 104.1 mg/dL (p < 0.0038), respectively. PKU patients also had lower levels of 22 LDL subclasses with the greatest differences in LDL2 Apo-B, LDL2 Particle Number, LDL2-phospholipids, and LDL2-cholesterol (p < 0.0001). There was a slight negative correlation of total cholesterol and LDL-cholesterol with concurrent Phe level. VLDL5-free cholesterol, VLDL5-cholesterol, VLDL5-phospholipids, and VLDL4-free cholesterol showed a significant (p < 0.05) negative correlation with concurrent Phe level. There was no difference in HDL and their subclasses between PKU patients and controls. Tyrosine, glutamine, and creatinine were significantly lower in PKU patients compared to controls, while citric and glutamic acids were significantly higher. Conclusions Using NMR spectroscopy, a unique lipoprotein profile in PKU patients can be demonstrated which mimics a non-atherogenic profile as seen in patients treated by statins.http://link.springer.com/article/10.1186/s13023-020-1329-5Adult PKUTreatmentCholesterolLipoprotein subclassesNMR |
| spellingShingle | Claire Cannet Andrea Pilotto Júlio César Rocha Hartmut Schäfer Manfred Spraul Daniela Berg Peter Nawroth Christian Kasperk Gwendolyn Gramer Dorothea Haas David Piel Stefan Kölker Georg Hoffmann Peter Freisinger Friedrich Trefz Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation Orphanet Journal of Rare Diseases Adult PKU Treatment Cholesterol Lipoprotein subclasses NMR |
| title | Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation |
| title_full | Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation |
| title_fullStr | Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation |
| title_full_unstemmed | Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation |
| title_short | Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation |
| title_sort | lower plasma cholesterol ldl cholesterol and ldl lipoprotein subclasses in adult phenylketonuria pku patients compared to healthy controls results of nmr metabolomics investigation |
| topic | Adult PKU Treatment Cholesterol Lipoprotein subclasses NMR |
| url | http://link.springer.com/article/10.1186/s13023-020-1329-5 |
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