{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T23:47:05Z","timestamp":1787615225252,"version":"build-2736575974"},"reference-count":36,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,4,19]],"date-time":"2022-04-19T00:00:00Z","timestamp":1650326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Long\u2010chain 3\u2010hydroxyacyl\u2010CoA dehydrogenase deficiency (LCHADD) is included in many newborn screening (NBS) programs. Acylcarnitine\u2010based NBS for LCHADD not only identifies LCHADD, but also the other deficiencies of the mitochondrial trifunctional protein (MTP), a multi\u2010enzyme complex involved in long\u2010chain fatty acid \u03b2\u2010oxidation. Besides LCHAD, MTP harbors two additional enzyme activities: long\u2010chain enoyl\u2010CoA hydratase (LCEH) and long\u2010chain ketoacyl\u2010CoA thiolase (LCKAT). Deficiency of one or more MTP activities causes generalized MTP deficiency (MTPD), LCHADD, LCEH deficiency (not yet reported), or LCKAT deficiency (LCKATD). To gain insight in the outcomes of MTP\u2010deficient patients diagnosed after the introduction of NBS for LCHADD in the Netherlands, a retrospective evaluation of genetic, biochemical, and clinical characteristics of MTP\u2010deficient patients, identified since 2007, was carried out. Thirteen patients were identified: seven with LCHADD, five with MTPD, and one with LCKATD. All LCHADD patients (one missed by NBS, clinical diagnosis) and one MTPD patient (clinical diagnosis) were alive. Four MTPD patients and one LCKATD patient developed cardiomyopathy and died within 1 month and 13\u2009months of life, respectively. Surviving patients did not develop symptomatic hypoglycemia, but experienced reversible cardiomyopathy and rhabdomyolysis. Five LCHADD patients developed subclinical neuropathy and\/or retinopathy. In conclusion, patient outcomes were highly variable, stressing the need for accurate classification of and discrimination between the MTP deficiencies to improve insight in the yield of NBS for LCHADD. NBS allowed the prevention of symptomatic hypoglycemia, but current treatment options failed to treat cardiomyopathy and prevent long\u2010term complications. Moreover, milder patients, who might benefit from NBS, were missed due to normal acylcarnitine profiles.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jimd.12502","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T12:25:36Z","timestamp":1649161536000},"page":"804-818","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Genetic, biochemical, and clinical spectrum of patients with mitochondrial trifunctional protein deficiency identified after the introduction of newborn screening in the Netherlands"],"prefix":"10.1002","volume":"45","author":[{"given":"Marit","family":"Schwantje","sequence":"first","affiliation":[{"name":"Department of Metabolic Diseases Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"},{"name":"Laboratory Genetic Metabolic Diseases, and Metabolism Institute, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine A.","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lonneke","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Amalia Children's Hospital Radboud University Medical Centre  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annet M.","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Metabolic Diseases, Emma Children's Hospital, and Metabolism Institute, Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Cuppen","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Wilhelmina Children's Hospital, University Medical Center Utrecht  Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenie","family":"Dekkers","sequence":"additional","affiliation":[{"name":"National Institute for Public Health and the Environment (RIVM) Reference Laboratory for Pre\u2010 and Neonatal Screening, Center for Health Protection (R.M.) and Center for Population Screening (E.D)  Bilthoven The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terry G. 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