{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T16:24:26Z","timestamp":1791649466357,"version":"4.3.4"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T00:00:00Z","timestamp":1654473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tyrosine hydroxylase deficiency (THD) is a treatable inborn error of dopamine biosynthesis caused by mutations in <jats:italic>TH<\/jats:italic>. Two presentations are described. Type A, milder, presents after 12\u2009months of age with progressive hypokinesis and rigidity. Type B presents before 12\u2009months as a progressive complex encephalopathy. We report a girl with mild THD who had recurrent episodes of neurological decompensations. Before the first episode, she had normal development except for mild head tremor. Episodes occurred at 12, 19, and 25\u2009months of age. After viral infections or vaccination, she developed lethargy, worsened tremor, language, and motor regression including severe axial hypotonia, recuperating over several weeks of intensive rehabilitation but with residual tremor and mild lower limb spasticity. Basal ganglia imaging was normal. Exome sequencing revealed two missense variants of uncertain significance in <jats:italic>TH<\/jats:italic>: c.1147G&gt;T and c.1084G&gt;A. Both have low gnomAD allele frequencies and in silico, are predicted to be deleterious. Cerebrospinal fluid analysis showed low homovanillic acid (HVA, 160\u2009nmol\/L, reference 233\u2013938) and low HVA\/5\u2010hydroxyindolacetic acid molar ratio (1.07, reference .5\u20133.5). She responded rapidly to L\u2010Dopa\/carbidopa without further episodes. Literature review revealed four other THD patients who had a total of seven episodes of marked hypotonia and motor regression following infections, occurring between ages 12\u2009months and 6\u2009years. All improved with L\u2010Dopa\/carbidopa treatment. Intermittent THD is treatable, important for genetic counseling, and should be considered after even a single episode of marked hypotonia with recuperation over weeks, especially in patients with preexisting tremor, dystonia, or rigidity.<\/jats:p>","DOI":"10.1002\/jmd2.12306","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T06:55:26Z","timestamp":1654584926000},"page":"400-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intermittent neurologic decompensation: An underrecognized presentation of tyrosine hydroxylase deficiency"],"prefix":"10.1002","volume":"63","author":[{"given":"Marjolaine","family":"Champagne","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Molecular Diagnostic Laboratory, Centre Hospitalier Universitaire Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella A.","family":"Horvath","sequence":"additional","affiliation":[{"name":"Division of Biochemical Diseases, Department of Pediatrics BC Children's Hospital  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Perreault","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Department of Pediatrics Centre Hospitalier Universitaire Sainte\u2010Justine  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Gauthier","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Molecular Diagnostic Laboratory, Centre Hospitalier Universitaire Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Integrated Centre for Pediatric Clinical Genomics, Centre Hospitalier Universitaire Sainte\u2010Justine  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Hyland","sequence":"additional","affiliation":[{"name":"MNG Laboratories (Medical Neurogenetics, LLC.), MNG, a Wholly Owned Subsidiary of Laboratory Corporation of America Holdings  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Fran\u00e7ois","family":"Soucy","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Molecular Diagnostic Laboratory, Centre Hospitalier Universitaire Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Integrated Centre for Pediatric Clinical Genomics, Centre Hospitalier Universitaire Sainte\u2010Justine  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grant A.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics, Molecular Diagnostic Laboratory, Centre Hospitalier Universitaire Sainte\u2010Justine Universit\u00e9 de Montr\u00e9al  Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Integrated Centre for Pediatric Clinical Genomics, Centre Hospitalier Universitaire Sainte\u2010Justine  Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40734-017-0065-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-0102(91)90001-F"},{"key":"e_1_2_8_4_1","unstructured":"Furukawa Y.&Kish S.Tyrosine Hydroxylase Deficiency. inGeneReviews\u00ae(eds. Adam M. P. et al.)(University of Washington Seattle 1993)."},{"key":"e_1_2_8_5_1","unstructured":"Striatal biopterin and tyrosine hydroxylase protein reduction in dopa\u2010responsive dystonia. PubMed NCBI.https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/10496263."},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.45.27235"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22565"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14624"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.10.014"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/practneurol-2015-001101"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq087"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152712800792866"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.20416"},{"key":"e_1_2_8_14_1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"Saudubray J","year":"2020"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-2011-11006"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073810377014"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/326707a0"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a122386"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12306","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmd2.12306","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T12:46:27Z","timestamp":1692449187000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,6]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/jmd2.12306"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12306","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,6]]},"assertion":[{"value":"2021-06-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}