{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:06:40Z","timestamp":1790276800307,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T00:00:00Z","timestamp":1554681600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","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":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Most infants with very\u2010long\u2010chain acyl\u2010CoA dehydrogenase deficiency (VLCADD) identified by newborn screening (NBS) are asymptomatic at the time of diagnosis and remain asymptomatic. If this outcome is due to prompt diagnosis and initiation of therapy, or because of identification of individuals with biochemical abnormalities who will never develop symptoms, is unclear. Therefore, a 10\u2010year longitudinal national cohort study of genetically confirmed VLCADD patients born before and after introduction of NBS was conducted. Main outcome measures were clinical outcome parameters, acyl\u2010CoA dehydrogenase very long chain gene analysis, VLCAD activity, and overall capacity of long\u2010chain fatty acid oxidation (LC\u2010FAO flux) in lymphocytes and cultured skin fibroblasts. Median VLCAD activity in lymphocytes of 54 patients, 21 diagnosed pre\u2010NBS and 33 by NBS was, respectively, 5.4% (95% confidence interval [CI]: 4.0\u20108.3) and 12.6% (95% CI: 10.7\u201017.7; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) of the reference mean. The median LC\u2010FAO flux was 33.2% (95% CI: 22.8\u201048.3) and 41% (95% CI: 40.8\u201068; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05) of the control mean, respectively. Clinical characteristics in 23 pre\u2010NBS and 37 NBS patients revealed hypoglycemic events in 12 vs 2 patients, cardiomyopathy in 5 vs 4 patients and myopathy in 14 vs 3 patients. All patients with LC\u2010FAO flux &lt;10% developed symptoms. Of the patients with LC\u2010FAO flux &gt;10% 7 out of 12 diagnosed pre\u2010NBS vs none by NBS experienced hypoglycemic events. NBS has a clear beneficial effect on the prevention of hypoglycemic events in patients with some residual enzyme activity, but does not prevent hypoglycemia nor cardiac complications in patients with very low residual enzyme activity. The effect of NBS on prevalence and prevention of myopathy\u2010related complications remains unclear.<\/jats:p>","DOI":"10.1002\/jimd.12075","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T05:19:05Z","timestamp":1550121545000},"page":"414-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Impact of newborn screening for very\u2010long\u2010chain acyl\u2010CoA dehydrogenase deficiency on genetic, enzymatic, and clinical outcomes"],"prefix":"10.1002","volume":"42","author":[{"given":"Jeannette C.","family":"Bleeker","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene L.","family":"Kok","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Dutch Fatty Acid Oxidation Expertise Center Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Department of Internal Medicine and Dermatology, Dietetics University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sacha","family":"Ferdinandusse","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Ludo","family":"van der Pol","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Rudolf Magnus Institute of Neuroscience, Spieren voor Spieren Kindercentrum, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Cuppen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Rudolf Magnus Institute of Neuroscience, Spieren voor Spieren Kindercentrum, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet M.","family":"Bosch","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Departments of Clinical Chemistry and Pediatrics Emma Children's Hospital, Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Langeveld","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Amsterdam UMC, University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry G. J.","family":"Derks","sequence":"additional","affiliation":[{"name":"Section of Metabolic Diseases Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Disorders, Department of Pediatrics Sophia Children's Hospital EMC  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot F.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Amsterdam UMC, Vrije Universiteit Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estela R.","family":"Gozalbo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Clinical Genomics Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique G. M.","family":"de Sain\u2010van der Velden","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Section Metabolic Diagnostics Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J.","family":"Rennings","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J. C. 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