{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T01:45:21Z","timestamp":1787190321056,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,1,6]],"date-time":"2020-01-06T00:00:00Z","timestamp":1578268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005941","name":"Dietmar Hopp Stiftung","doi-asserted-by":"publisher","award":["1"],"award-info":[{"award-number":["1"]}],"id":[{"id":"10.13039\/501100005941","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010441","name":"Medizinischen Fakult\u00e4t Heidelberg, Universit\u00e4t Heidelberg","doi-asserted-by":"publisher","award":["2"],"award-info":[{"award-number":["2"]}],"id":[{"id":"10.13039\/501100010441","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":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aromatic <jats:sc>l<\/jats:sc>\u2010amino\u2010acid decarboxylase (AADC) deficiency is an inherited disorder of biogenic amine metabolism with a broad neurological phenotype. The clinical symptoms overlap with other diseases resulting in an often delayed diagnosis. Innovative disease\u2010changing treatment options, particularly gene therapy, have emphasised the need for an early diagnosis. We describe the first method for 3\u2010<jats:italic>O<\/jats:italic>\u2010methyldopa (3\u2010OMD) analysis in dried blood spots (DBS) suitable for high throughput newborn screening (NBS). We established a novel tandem mass spectrometry method to quantify 3\u2010OMD in DBS and successfully tested it in 38\u2009888 unaffected newborns, 14 heterozygous <jats:italic>DDC<\/jats:italic> variant carriers, seven known AADC deficient patients, and 1079 healthy control subjects. 3\u2010OMD concentrations in 38\u2009888 healthy newborns revealed a mean of 1.16\u2009\u03bcmol\/L (SD = 0.31, range 0.31\u20104.6 \u03bcmol\/L). 1079 non\u2010AADC control subjects (0\u201018\u2009years) showed a mean 3\u2010OMD concentration of 0.78\u2009\u03bcmol\/L (SD = 1.75, range 0.24\u20102.36\u2009\u03bcmol\/L) with a negative correlation with age. Inter\u2010 and intra\u2010assay variability was low, and 3\u2010OMD was stable over 32\u2009days under different storage conditions. We identified seven confirmed AADC deficient patients (mean 3\u2010OMD 9.88\u2009\u03bcmol\/L [SD = 13.42, range 1.82\u201036.93\u2009\u03bcmol\/L]). The highest concentration of 3\u2010OMD was found in a NBS filter card of a confirmed AADC deficient patient with a mean 3\u2010OMD of 35.95\u2009\u03bcmol\/L. 14 <jats:italic>DDC<\/jats:italic> variant carriers showed normal 3\u2010OMD concentrations. We demonstrate a novel high\u2010throughput method to measure 3\u2010OMD in DBS, which allows integration in existing NBS programs enabling early diagnosis of AADC deficiency.<\/jats:p>","DOI":"10.1002\/jimd.12208","type":"journal-article","created":{"date-parts":[[2019,12,18]],"date-time":"2019-12-18T09:29:05Z","timestamp":1576661345000},"page":"602-610","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["High throughput newborn screening for aromatic \u029f\u2010amino\u2010acid decarboxylase deficiency by analysis of concentrations of 3\u2010<i>O<\/i>\u2010methyldopa from dried blood spots"],"prefix":"10.1002","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6909-0003","authenticated-orcid":false,"given":"Heiko","family":"Brennenstuhl","sequence":"first","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Kohlm\u00fcller","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn","family":"Gramer","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Syrbe","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Feyh","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen G.","family":"Okun","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4349-7662","authenticated-orcid":false,"given":"Thomas","family":"Opladen","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Division of Neuropediatrics and Metabolic Medicine University Children's Hospital  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2008.03.008"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0522-z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi120"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2016.09.006"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003640"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy331"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25467"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.01.034"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.05.011"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-199509000-00009"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-6-44"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(17)30125-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmr.2011.09.022"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.11.068"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2214\/AJR.11.7849"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-007-9442-6"},{"issue":"2","key":"e_1_2_10_18_1","first-page":"S32","article-title":"Problems 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