{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T03:34:41Z","timestamp":1794454481723,"version":"4.9.1"},"reference-count":35,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND:<\/jats:title>\n                  <jats:p>Although extended newborn screening (NBS) programs have been introduced more than 20 years ago, their impact on the long-term clinical outcome of individuals with inherited metabolic diseases (IMDs) is still rarely investigated.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS:<\/jats:title>\n                  <jats:p>We studied the clinical outcomes of individuals with IMDs identified by NBS between 1999 and 2016 in a prospective multicenter observational study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS:<\/jats:title>\n                  <jats:p>In total, 306 screened individuals with IMDs (115 with phenylketonuria and 191 with other IMDs with a lifelong risk for metabolic decompensation) were followed for a median time of 6.2 years. Although the risk for metabolic decompensation was disease-specific and NBS could not prevent decompensations in every individual at risk (n = 49), the majority did not develop permanent disease-specific signs (75.9%), showed normal development (95.6%) and normal cognitive outcome (87.7%; mean IQ: 100.4), and mostly attended regular kindergarten (95.2%) and primary school (95.2%). This demonstrates that not only individuals with phenylketonuria, serving as a benchmark, but also those with lifelong risk for metabolic decompensation had a favorable long-term outcome. High NBS process quality is the prerequisite of this favorable outcome. This is supported by 28 individuals presenting with first symptoms at a median age of 3.5 days before NBS results were available, by the absence of neonatal decompensations after the report of NBS results, and by the challenge of keeping relevant process parameters at a constantly high level.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS:<\/jats:title>\n                  <jats:p>NBS for IMDs, although not completely preventing clinical presentations in all individuals, can be considered a highly successful program of secondary prevention.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2020-0444","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T12:25:31Z","timestamp":1602591931000},"source":"Crossref","is-referenced-by-count":73,"title":["Long-term Outcomes of Individuals With Metabolic Diseases Identified Through Newborn Screening"],"prefix":"10.1542","volume":"146","author":[{"given":"Ulrike","family":"M\u00fctze","sequence":"first","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven F.","family":"Garbade","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn","family":"Gramer","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Lindner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, University Children\u2019s Hospital Frankfurt, Frankfurt, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Freisinger","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Reutlingen, Klinikum am Steinenberg Reutlingen, Reutlingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Catharina","family":"Gr\u00fcnert","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Hennermann","sequence":"additional","affiliation":[{"name":"Villa Metabolica, Center for Pediatric and Adolescent Medicine, University Medical Center Mainz, Mainz, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Ensenauer","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children\u2019s Hospital, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany;"},{"name":"Institute of Child Nutrition, Max Rubner-Institut, Karlsruhe, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Thimm","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children\u2019s Hospital, Heinrich Heine University D\u00fcsseldorf, D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Zirnbauer","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine, Medical School, Ulm University, Ulm, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leichsenring","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Medicine, Medical School, Ulm University, Ulm, Germany; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gleich","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friederike","family":"H\u00f6rster","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Grohmann-Held","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"},{"name":"Center for Child and Adolescent Medicine, University Hospital Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolas","family":"Boy","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmin","family":"Fang-Hoffmann","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Burgard","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Walter","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"K\u00f6lker","sequence":"additional","affiliation":[{"name":"Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2020,11,1]]},"reference":[{"issue":"23","key":"2021121012550546300_B1","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1056\/NEJMoa025225","article-title":"Screening newborns for inborn errors of metabolism by tandem mass spectrometry","volume":"348","author":"Wilcken","year":"2003","journal-title":"N Engl J Med"},{"issue":"6 pt 1","key":"2021121012550546300_B2","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1542\/peds.111.6.1399","article-title":"Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications","volume":"111","author":"Schulze","year":"2003","journal-title":"Pediatrics"},{"issue":"5 pt 2","key":"2021121012550546300_B3","first-page":"S296","article-title":"Newborn screening: toward a uniform screening panel and system\u2013executive summary","volume":"117","author":"American College of Medical Genetics Newborn Screening Expert Group","year":"2006","journal-title":"Pediatrics"},{"key":"2021121012550546300_B4","volume-title":"Principles and Practice of Screening for Disease","author":"Wilson","year":"1968"},{"issue":"4","key":"2021121012550546300_B5","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s10545-012-9483-0","article-title":"Newborn screening programmes in Europe; 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