{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:53:51Z","timestamp":1791928431495,"version":"4.3.4"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tyrosine hydroxylase deficiency (THD) is a rare autosomal recessive disorder caused by impaired catecholamine biosynthesis in the brain. The rarity and heterogeneous clinical spectrum of THD often lead to misdiagnosis, and evidence\u2010based, genotype\u2010specific levodopa dosing protocols remain unavailable.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To delineate the clinical spectrum, genetic variants, and levodopa response in a large single\u2010center cohort of Chinese pediatric THD patients, and to explore genotype\u2010specific dosing requirements.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was performed on 51 pediatric patients diagnosed with THD at a single center in China. Data on genotype, phenotype, and treatment outcomes were reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Movement disorders were present in 96.1% of cases, with developmental delay observed in 88.2%, and autonomic symptoms in 51.0%. Among the 36 identified variants, the predominant were p.R233H (37.3%), p.R153X (10.8%), and p.Q232X (6.9%). Among the 13 p.R233H carriers who showed a good response to levodopa, those with a nonsense second allele (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20095) required a significantly higher mean levodopa dose than those with a missense second allele (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20098) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study is the largest retrospective analysis of pediatric THD patients from a single\u2010ethnicity\u00a0cohort, summarizing the clinical and genotypic characteristics. Variant type\u2010particularly R233H\/nonsense versus R233H\/missense significantly influences dose requirements, underscoring the value of genotype\u2010guided, dynamic levodopa titration to optimize long\u2010term outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mdc3.70371","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T07:06:30Z","timestamp":1761116790000},"page":"907-913","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phenotypic, Genotypic Characteristics, and Treatment Strategies of Pediatric Tyrosine Hydroxylase Deficiency: A Single\u2010Center Retrospective Analysis of 51 Cases"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4520-5056","authenticated-orcid":false,"given":"Tingting","family":"Ban","sequence":"first","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"},{"name":"Department of Neurology Children's Hospital of Fudan University, Xiamen Branch (Xiamen Children's Hospital)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"},{"name":"Department of Neurology Children's Hospital of Fudan University, Xiamen Branch (Xiamen Children's Hospital)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caimei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology Children's Hospital of Fudan University, Xiamen Branch (Xiamen Children's Hospital)  Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghe","family":"Xing","sequence":"additional","affiliation":[{"name":"Children's Hospital of Fudan University and Institutes of Biomedical Sciences of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuizhen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Neurology, National Children's Medical Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28874"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.1004307"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq087"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11111186"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2101035"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2020.00083"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.70202"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-52014-2.00039-2"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21199"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-57733-6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000021753"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12702"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38323-w"},{"issue":"8","key":"e_1_2_9_15_1","first-page":"574","article-title":"Clinical features and genetic characteristics of children with tyrosine hydroxylase deficiency caused by TH gene variants","volume":"36","year":"2021","journal-title":"Chin J Appl Clin Pediatr"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.644910"},{"issue":"10","key":"e_1_2_9_17_1","first-page":"1047","article-title":"Clinical analysis of nine infants with tyrosine hydroxylase deficiency","volume":"54","author":"Zhang Y","year":"2021","journal-title":"Chin J Neurol"}],"container-title":["Movement Disorders Clinical 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