{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:13:37Z","timestamp":1792793617155,"version":"4.5.0"},"reference-count":13,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2000,12,1]],"date-time":"2000-12-01T00:00:00Z","timestamp":975628800000},"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":[[2000,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tyrosine hydroxylase (TH) deficiency is generally considered as a cause of the autosomal recessive form of dopa\u2010responsive dystonia, also known as Segawa disease. Clinical hallmarks comprise parkinsonian and other extrapyramidal symptoms. Biochemically the defect leads to the defective synthesis of catecholamines, in particular dopamine. The diagnosis relies on a characteristic pattern of biogenic amine metabolites exclusively in the CSF and can be confirmed by establishing a mutation in the TH gene. Here we present a patient meeting all diagnostic criteria, including a new homozygous mutation (926T&gt;C) with confirmed parental heterozygosity, extrapyramidal symptoms, but atypical other symptoms with periodic neurological episodes observed every 4 days and unresponsive to dopa treatment. The CSF biochemical abnormalities were severe. Uncharacteristically, a strongly abnormal urinary catecholamine metabolite pattern was also consistently observed. The atypical presentation of this patient shows that the clinical and metabolic phenotype of TH deficiency is more variable than formerly thought, and that the condition should no longer be considered as a treatable disorder <jats:italic>per se<\/jats:italic>.<\/jats:p>","DOI":"10.1023\/a:1026760602577","type":"journal-article","created":{"date-parts":[[2003,11,6]],"date-time":"2003-11-06T18:09:07Z","timestamp":1068142147000},"page":"819-825","source":"Crossref","is-referenced-by-count":40,"title":["Tyrosine hydroxylase deficiency unresponsive to L\u2010dopa treatment with unusual clinical and biochemical presentation"],"prefix":"10.1002","volume":"23","author":[{"given":"P.","family":"De Lonlay","sequence":"first","affiliation":[{"name":"D\u00e9partment de P\u00e9diatrie H\u00f4pital Necker\u2010Enfants Malades  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. C.","family":"Nassogne","sequence":"additional","affiliation":[{"name":"D\u00e9partment de P\u00e9diatrie H\u00f4pital Necker\u2010Enfants Malades  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H.","family":"van Gennip","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Netherlands"},{"name":"Departments of Clinical Chemistry Emma Children's Hospital  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. C.","family":"van Cruchten","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Netherlands"},{"name":"Departments of Clinical Chemistry Emma Children's Hospital  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Billette de Villemeur","sequence":"additional","affiliation":[{"name":"Service de Neurologie P\u00e9diatrique H\u00f4pital Trousseau  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Cretz","sequence":"additional","affiliation":[{"name":"Service de P\u00e9diatrie H\u00f4pital de Colmar  Colmar France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Stoll","sequence":"additional","affiliation":[{"name":"Service de G\u00e9n\u00e9tique  Strasbourg"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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M.","family":"Abeling","sequence":"additional","affiliation":[{"name":"Academic Medical Center University of Amsterdam  Netherlands"},{"name":"Departments of Clinical Chemistry Emma Children's Hospital  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2000,12]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(84)90181-5"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005307919767"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/44.9.1897"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/45.12.2073"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/38.12.2405"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.10.1980"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.7.1209"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00225091"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.7.1023"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.38.7.666"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/36.10.1834"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050756"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005539803576"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1023%2FA%3A1026760602577","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1023\/A%3A1026760602577","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T20:28:21Z","timestamp":1694809701000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1023\/A%3A1026760602577"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,12]]},"references-count":13,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2000,12]]}},"alternative-id":["10.1023\/A:1026760602577"],"URL":"https:\/\/doi.org\/10.1023\/a:1026760602577","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,12]]}}}