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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\u2009years) and 14 healthy controls (mean age 35.2\u2009years), 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\u2009MHz Bruker AVANCE IVDr spectrometer as previously described.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Concurrent plasma Phe in PKU patients showed a wide range with a mean of 899\u2009\u03bcmol\/L (50\u20131318\u2009\u03bcmol\/L). Total cholesterol and LDL-cholesterol were significantly lower in PKU patients versus controls: 179.4 versus 200.9\u2009mg\/dL (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.02) and 79.5 versus 104.1\u2009mg\/dL (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0038), 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 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.0001). 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 (<jats:italic>p<\/jats:italic>\u00a0&lt;\u20090.05) 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.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s13023-020-1329-5","type":"journal-article","created":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T19:03:33Z","timestamp":1582830213000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Lower plasma cholesterol, LDL-cholesterol and LDL-lipoprotein subclasses in adult phenylketonuria (PKU) patients compared to healthy controls: results of NMR metabolomics investigation"],"prefix":"10.1186","volume":"15","author":[{"given":"Claire","family":"Cannet","sequence":"first","affiliation":[]},{"given":"Andrea","family":"Pilotto","sequence":"additional","affiliation":[]},{"given":"J\u00falio C\u00e9sar","family":"Rocha","sequence":"additional","affiliation":[]},{"given":"Hartmut","family":"Sch\u00e4fer","sequence":"additional","affiliation":[]},{"given":"Manfred","family":"Spraul","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Berg","sequence":"additional","affiliation":[]},{"given":"Peter","family":"Nawroth","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Kasperk","sequence":"additional","affiliation":[]},{"given":"Gwendolyn","family":"Gramer","sequence":"additional","affiliation":[]},{"given":"Dorothea","family":"Haas","sequence":"additional","affiliation":[]},{"given":"David","family":"Piel","sequence":"additional","affiliation":[]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[]},{"given":"Georg","family":"Hoffmann","sequence":"additional","affiliation":[]},{"given":"Peter","family":"Freisinger","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-7463","authenticated-orcid":false,"given":"Friedrich","family":"Trefz","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"issue":"2","key":"1329_CR1","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1542\/peds.2009-3584","volume":"126","author":"F Feillet","year":"2010","unstructured":"Feillet F, van Spronsen FJ, MacDonald A, Trefz FK, Demirkol M, Giovannini M, et al. 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