{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:16:21Z","timestamp":1792174581012,"version":"4.4.0"},"reference-count":17,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2000,9,1]],"date-time":"2000-09-01T00:00:00Z","timestamp":967766400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2000,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies using <jats:italic>in vivo<\/jats:italic> proton magnetic resonance spectroscopy (<jats:sup>1<\/jats:sup>H MRS) have suggested that plasma phenylalanine (Phe) may not be a reliable indicator of brain Phe level in subjects with phenylketonuria (PKU). Interindividual variation in cerebral Phe can contribute to the phenotypic variability of the disease. We report the results of the direct assessment of brain Phe by <jats:italic>1<\/jats:italic>H MRS in 10 off\u2010diet PKU patients (aged 15.5\u201330.5 years), 4 detected and treated early, 6 late. In a single patient, brain Phe was evaluated before and 15 days after diet discontinuation. FLAIR MRI and <jats:sup>1<\/jats:sup>H MRS were performed in the same setting by a 1.5 T clinical MR scanner. MR images were scored according to the extent of the lobar white\u2010matter hyperintensity. Brain <jats:sup>1<\/jats:sup>H MRS Phe signal (resonating at 7.36 ppm) was evaluated as a ratio to the creatine+phosphocreatine signal. Brain Phe was correlated with clinical, biochemical and MRI findings. Results were as follows. (1) An abnormal concentration of brain Phe was detected in all 10 PKU subjects (ranging from 0.030 to 0.074), associated with a wide interindividual variability of concurrent plasma Phe (ranging from 724 to 2800 \u03bcmol\/L). (2) In late\u2010detected subjects, brain Phe concentration correlated with clinical phenotype better than did plasma Phe. The discrepancy between brain and plasma Phe was relevant from a clinical point of view in two cases: in one, a late\u2010detected patient with normal mental development, a high level of plasma Phe was associated with a relatively low concentration of brain Phe; in the other, a late\u2010detected subject with severe neurological impairment, a very high level of brain Phe was associated with plasma Phe compatible with the diagnosis of mild PKU. (3) White\u2010matter alterations were detected in all patients. FLAIR MRI sequences disclosed an involvement of optic chiasma and tracts in 7 subjects. No correlation was found between white\u2010matter alterations and concurrent brain Phe concentrations. (4) In the only case assessed under different intake of Phe, the relevant increase of brain Phe paralleled the concurrent increase of plasma Phe, showing that <jats:sup>1<\/jats:sup>H MRS can be a useful tool in evaluating the individual vulnerability of PKU patients to different values of plasma Phe.<\/jats:p>","DOI":"10.1023\/a:1005621727560","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T23:07:17Z","timestamp":1040512037000},"page":"563-570","source":"Crossref","is-referenced-by-count":39,"title":["Clinical significance of brain phenylalanine concentration assessed by in vivo proton magnetic resonance spectroscopy in phenylketonuria"],"prefix":"10.1002","volume":"23","author":[{"given":"V.","family":"Leuzzi","sequence":"first","affiliation":[{"name":"Dipartimento di Scienze Neurologiche e Psichiatriche dell'Et\u00e0 Evolutiva Universit\u00e0 \u2018La Sapienza\u2019  Rome"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Bianchi","sequence":"additional","affiliation":[{"name":"U.O. Neuroradiologia Ospedale S. Chiara  Pisa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Tosetti","sequence":"additional","affiliation":[{"name":"IRCCS \u2018Stella Maris\u2019  Pisa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl.","family":"Carducci","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale. Universit\u00e0 \u2018La Sapienza\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ca.","family":"Carducci","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale. Universit\u00e0 \u2018La Sapienza\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Antonozzi","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Sperimentale. Universit\u00e0 \u2018La Sapienza\u2019  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,9]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199006000-00005"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004310051008"},{"key":"e_1_2_1_4_1","first-page":"16","article-title":"Hyperphenylalaninemia. Diagnosis and classi\u00a2cation of the various types of phenylalanine hydroxylase","volume":"281","author":"G\u00cfttler F","year":"1980","journal-title":"Acta Paediatr Suppl."},{"key":"e_1_2_1_5_1","first-page":"143","article-title":"Atypical phenylketonuria with borderline or normal intelligence","volume":"116","author":"Hsia DY\u2010Y","year":"1968","journal-title":"Am J Dis Child"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02436753"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1940040214"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1071561"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02436009"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410430215"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)01054-8"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199811000-00004"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199502000-00020"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.201.2.8888233"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5017"},{"key":"e_1_2_1_16_1","first-page":"239","article-title":"Phenylketonuria with normal intelligence","volume":"27","author":"Primrose DA","year":"1983","journal-title":"J Ment De\u00a2c Res"},{"key":"e_1_2_1_17_1","first-page":"1015","volume-title":"The Molecular and Metabolic Bases of Inherited Disease","author":"Scriver CR","year":"1995"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/116.4.811"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1023%2FA%3A1005621727560","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1023\/A%3A1005621727560","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T22:44:12Z","timestamp":1694817852000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1023\/A%3A1005621727560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,9]]},"references-count":17,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2000,9]]}},"alternative-id":["10.1023\/A:1005621727560"],"URL":"https:\/\/doi.org\/10.1023\/a:1005621727560","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,9]]}}}