{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:16:41Z","timestamp":1791951401094,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1U54NS115198\u201001"],"award-info":[{"award-number":["1U54NS115198\u201001"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016650","name":"Rare Diseases Clinical Research Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016650","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mono\u2010allelic\n                    <jats:italic>DHDDS<\/jats:italic>\n                    variants are associated with seizures, intellectual disability, and movement disorders. The age of onset and progression rates of symptoms vary greatly among patients, spanning from infancy to late adulthood. Yet, the reasons behind this clinical variability and the underlying pathophysiological mechanisms of the disease have remained elusive. We investigated the age of onset and the progression of symptoms over time in 59 patients with heterozygous\n                    <jats:italic>DHDDS<\/jats:italic>\n                    variants, drawing from medical literature and incorporating five previously unreported cases from the FCDGC Natural History Study. Clinical symptoms typically emerged early in life. Ataxia, tremor, dystonia, and dyskinesia manifested slightly later in childhood. Global developmental delay usually presented as the initial symptom. We observed diverse rates of symptom accumulation over time: some patients exhibited the full spectrum of symptoms in early childhood, while others developed novel symptoms well into adulthood. Interestingly, neither the sex nor the underlying\n                    <jats:italic>DHDDS<\/jats:italic>\n                    variants correlated with the age of symptom onset or specific clinical symptoms. Additionally, we found that 19% of patients presented with autism spectrum disorder. This study offers insight into the age of symptom onset and the rate of symptom accumulation in patients with\n                    <jats:italic>DHDDS<\/jats:italic>\n                    variants. We found no correlation between the age of onset and progression of clinical symptoms with specific\n                    <jats:italic>DHDDS<\/jats:italic>\n                    variants or patient sex. Autism spectrum disorder is common in patients and warrants attention in clinical management.\n                  <\/jats:p>","DOI":"10.1002\/jimd.12769","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T02:39:11Z","timestamp":1719023951000},"page":"935-944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Assessing age of onset and clinical symptoms over time in patients with heterozygous pathogenic\n                    <scp>DHDDS<\/scp>\n                    variants"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4335-5034","authenticated-orcid":false,"given":"I. J. J.","family":"Muffels","sequence":"first","affiliation":[{"name":"Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sadek","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6915-4364","authenticated-orcid":false,"given":"T.","family":"Kozicz","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Anatomy University of Pecs Medical School  Pecs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7441-700X","authenticated-orcid":false,"given":"E.","family":"Morava","sequence":"additional","affiliation":[{"name":"Department of Genetics and Genomics Icahn School of Medicine at Mount Sinai  New York New York USA"},{"name":"Department of Biophysics University of Pecs Medical School  Pecs Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2008381117"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.739490"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.01.002"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.09.008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.737094"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1086\/512130"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.13920"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab299"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01137-6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.03.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/epi4.12350"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2021.05.010"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2022.04.002"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2023.5051"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.su7102a1"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.ss7202a1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.2021.100"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1177\/003335490612100314"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9325-5"},{"key":"e_1_2_8_21_1","article-title":"Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease","volume":"10","author":"Vignogna RC","year":"2022","journal-title":"Elife"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021004"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.12769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T07:25:12Z","timestamp":1731569112000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.12769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,21]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["10.1002\/jimd.12769"],"URL":"https:\/\/doi.org\/10.1002\/jimd.12769","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,21]]},"assertion":[{"value":"2024-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}