{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:54:23Z","timestamp":1793346863677,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>National newborn screening programmes based on tandem-mass spectrometry (MS\/MS) and other newborn screening (NBS) technologies show a substantial variation in number and types of disorders included in the screening panel. Once established, these methods offer the opportunity to extend newborn screening panels without significant investment and cost. However, systematic evaluations of newborn screening programmes are rare, most often only describing parts of the whole process from taking blood samples to long-term evaluation of outcome.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>In a prospective single screening centre observational study 373 cases with confirmed diagnosis of a metabolic disorder from a total cohort of 1,084,195 neonates screened in one newborn screening laboratory between January 1, 1999, and June 30, 2009 and subsequently treated and monitored in five specialised centres for inborn errors of metabolism were examined. Process times for taking screening samples, obtaining results, initiating diagnostic confirmation and starting treatment as well as the outcome variables metabolic decompensations, clinical status, and intellectual development at a mean age of 3.3 years were evaluated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Optimal outcome is achieved especially for the large subgroup of patients with medium-chain acyl-CoA dehydrogenase deficiency. Kaplan-Meier-analysis revealed disorder related patterns of decompensation. Urea cycle disorders, organic acid disorders, and amino acid disorders show an early high and continuous risk, medium-chain acyl-CoA dehydrogenase deficiency a continuous but much lower risk for decompensation, other fatty acid oxidation disorders an intermediate risk increasing towards the end of the first year. Clinical symptoms seem inevitable in a small subgroup of patients with very early disease onset. Later decompensation can not be completely prevented despite pre-symptomatic start of treatment. Metabolic decompensation does not necessarily result in impairment of intellectual development, but there is a definite association between the two.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Physical and cognitive outcome in patients with presymptomatic diagnosis of metabolic disorders included in the current German screening panel is equally good as in phenylketonuria, used as a gold standard for NBS. Extended NBS entails many different interrelated variables which need to be carefully evaluated and optimized. More reports from different parts of the world are needed to allow a comprehensive assessment of the likely benefits, harms and costs in different populations.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1750-1172-6-44","type":"journal-article","created":{"date-parts":[[2011,6,21]],"date-time":"2011-06-21T06:48:26Z","timestamp":1308638906000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":144,"title":["Efficacy and outcome of expanded newborn screening for metabolic diseases - Report of 10 years from South-West Germany *"],"prefix":"10.1186","volume":"6","author":[{"given":"Martin","family":"Lindner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendolyn","family":"Gramer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Haege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmin","family":"Fang-Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl O","family":"Schwab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Tacke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich K","family":"Trefz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugen","family":"Mengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Wendel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Leichsenring","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Burgard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg F","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,6,20]]},"reference":[{"key":"308_CR1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1097\/GIM.0b013e31817b80fd","volume":"10","author":"MS Watson","year":"2008","unstructured":"Watson MS, Epstein C, Howell RR, Jones MC, Korf BR, McCabe ER, Simpson JL: Developing a national collaborative study system for rare genetic diseases. Genet Med. 2008, 10: 325-329. 10.1097\/GIM.0b013e31817b80fd.","journal-title":"Genet Med"},{"key":"308_CR2","doi-asserted-by":"crossref","first-page":"S296","DOI":"10.1542\/peds.2005-2633I","volume":"117","author":"American College of Medical Genetics Newborn Screening Expert Group","year":"2006","unstructured":"American College of Medical Genetics Newborn Screening Expert Group: Newborn screening: Toward a Uniform Screening Panel and System-Executive Summary. Pediatrics. 2006, 117: S296-S307.","journal-title":"Pediatrics"},{"key":"308_CR3","volume-title":"Lebensjahres (Kinder-Richtlinien) zur Einf\u00fchrung des erweiterten Neugeborenen-Screenings","author":"Gemeinsamer Bundesausschuss der \u00c4rzte und Krankenkassen","year":"2005","unstructured":"Gemeinsamer Bundesausschuss der \u00c4rzte und Krankenkassen: Beschluss \u00fcber eine \u00c4nderung der Richtlinen des Bundesausschusses der \u00c4rzte und Krankenkassen \u00fcber die Fr\u00fcherkennung von Krankheiten bei Kindern bis zur Vollendung des 6. Lebensjahres (Kinder-Richtlinien) zur Einf\u00fchrung des erweiterten Neugeborenen-Screenings, 2005. (Accessed May 18, 2011, at http:\/\/www.g-ba.de\/informationen\/beschluesse\/zur-richtlinie\/15\/#170)."},{"key":"308_CR4","volume-title":"NHS Newborn Bloodspot Screening Programme.","author":"UK Newborn Screening Programme Centre","year":"2011","unstructured":"UK Newborn Screening Programme Centre: NHS Newborn Bloodspot Screening Programme. (Accessed May 18, 2011 at http:\/\/newbornbloodspot.screening.nhs.uk)."},{"key":"308_CR5","unstructured":"Association Fran\u00e7aise pour le D\u00e9pistage et la Pr\u00e9vention des Handicaps de l'Enfant. (Accessed May 18, 2011 at http:\/\/www.afdphe.fr)."},{"key":"308_CR6","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1007\/s10545-007-0687-7","volume":"30","author":"CD Padilla","year":"2007","unstructured":"Padilla CD, Therrell BL: Newborn screening in the Asia Pacific region. J Inherit Metab Dis. 2007, 30: 490-506. 10.1007\/s10545-007-0687-7.","journal-title":"J Inherit Metab Dis"},{"key":"308_CR7","volume-title":"Principles and Practice of Screening for Disease","author":"JMG Wilson","year":"1968","unstructured":"Wilson JMG, Jungner G: Principles and Practice of Screening for Disease. Geneva, Switzerland: World Health Organization; 1968, Public Health Papers, No. 34."},{"key":"308_CR8","volume-title":"An Ethical Analysis by The President's Council on Bioethics","author":"The President's Council on Bioethics","year":"2008","unstructured":"The President's Council on Bioethics 2008. The Changing Moral Focus of Newborn Screening: An Ethical Analysis by The President's Council on Bioethics, Washington, DC, December 2008, Accessed May 18, 2011 at [http:\/\/bioethics.georgetown.edu\/pcbe\/reports\/newborn_screening]."},{"key":"308_CR9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1159\/000272898","volume":"14","author":"A Andermann","year":"2011","unstructured":"Andermann A, Blancquaert I, Beauchamp S, Costea I: Guiding Policy Decisions for Genetic Screening: Developing a Systematic and Transparent Approach. Public Health Genomics. 2011, 14: 9-16. 10.1159\/000272898.","journal-title":"Public Health Genomics"},{"issue":"4","key":"308_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.2471\/BLT.07.050112","volume":"86","author":"A Andermann","year":"2008","unstructured":"Andermann A, Blancquaert I, Beauchamp S, D\u00e9ry V: Revisiting Wilson and Jungner in the genomic age: a review of screening criteria over the past 40 years. Bull World Health Organ. 2008, 86 (4): 317-319. 10.2471\/BLT.07.050112.","journal-title":"Bull World Health Organ"},{"key":"308_CR11","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1007\/s00112-002-0611-z","volume":"150","author":"E Harms","year":"2002","unstructured":"Harms E, Roscher A, Gr\u00fcters A, Heinrich U, Genzel-Borovicz\u00e9ny O, Rossi R, Schulze A, Zabransky S: Neue Screening-Richtlinien - Richtlinien zur Organisation und Durchf\u00fchrung des Neugeborenenscreenings auf angeborene Stoffwechselst\u00f6rungen und Endokrinopathien in Deutschland. Monatsschr Kinderheilkd. 2002, 150: 1424-1440. 10.1007\/s00112-002-0611-z.","journal-title":"Monatsschr Kinderheilkd"},{"key":"308_CR12","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1542\/peds.111.6.1399","volume":"111","author":"A Schulze","year":"2003","unstructured":"Schulze A, Lindner M, Kohlm\u00fcller D, Olgem\u00f6ller K, Mayatepek E, Hoffmann GF: Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics. 2003, 111: 1399-1406. 10.1542\/peds.111.6.1399.","journal-title":"Pediatrics"},{"key":"308_CR13","doi-asserted-by":"publisher","first-page":"e241","DOI":"10.1542\/peds.2008-0586","volume":"124","author":"B Wilcken","year":"2009","unstructured":"Wilcken B, Haas M, Joy P, Wiley V, Bowling F, Carpenter K, Christodoulou J, Cowley D, Ellaway C, Fletcher J, Kirk EP, Lewis B, McGill J, Peters H, Pitt J, Ranieri E, Yaplito-Lee J, Boneh A: Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics. 2009, 124: e241-248. 10.1542\/peds.2008-0586.","journal-title":"Pediatrics"},{"issue":"2","key":"308_CR14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.ymgme.2004.12.010","volume":"85","author":"U Nennstiel-Ratzel","year":"2005","unstructured":"Nennstiel-Ratzel U, Arenz S, Maier EM, Knerr I, Baumk\u00f6tter J, R\u00f6schinger W, Liebl B, Hadorn HB, Roscher AA, von Kries R: Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A >G identified by neonatal screening. Mol Genet Metab. 2005, 85 (2): 157-159. 10.1016\/j.ymgme.2004.12.010.","journal-title":"Mol Genet Metab"},{"key":"308_CR15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S0140-6736(07)60029-4","volume":"369","author":"B Wilcken","year":"2007","unstructured":"Wilcken B, Haas M, Joy P, Wiley V, Chaplin M, Black C, Fletcher J, McGill J, Boneh A: Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet. 2007, 369: 37-42. 10.1016\/S0140-6736(07)60029-4.","journal-title":"Lancet"},{"key":"308_CR16","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1136\/adc.79.2.116","volume":"79","author":"RJ Pollitt","year":"1998","unstructured":"Pollitt RJ, Leonard JV: Prospective surveillance study of medium chain acyl-CoA dehydrogenase deficiency in the UK. Arch Dis Child. 1998, 79: 116-119. 10.1136\/adc.79.2.116.","journal-title":"Arch Dis Child"},{"key":"308_CR17","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.jpeds.2005.12.028","volume":"148","author":"TG Derks","year":"2006","unstructured":"Derks TG, Reijngoud DJ, Waterham HR, Gerver WJ, van den Berg MP, Sauer PJ, Smit GP: The natural history of medium-chain acyl CoA dehydrogenase deficiency in the Netherlands: clinical presentation and outcome. J Pediatr. 2006, 148: 665-670. 10.1016\/j.jpeds.2005.12.028.","journal-title":"J Pediatr"},{"key":"308_CR18","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1136\/adc.70.5.410","volume":"70","author":"B Wilcken","year":"1994","unstructured":"Wilcken B, Hammond J, Silink M: Morbidity and mortality in medium chain acyl coenzyme A dehydrogenase deficiency. Arch Dis Child. 1994, 70: 410-412. 10.1136\/adc.70.5.410.","journal-title":"Arch Dis Child"},{"key":"308_CR19","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1203\/01.pdr.0000219387.79887.86","volume":"59","author":"S K\u00f6lker","year":"2006","unstructured":"K\u00f6lker S, Garbade SF, Greenberg CR, Leonard JV, Saudubray JM, Ribes A, Kalkanoglu HS, Lund AM, Merinero B, Wajner M, Troncoso M, Williams M, Walter JH, Campistol J, Mart\u00ed-Herrero M, Caswill M, Burlina AB, Lagler F, Maier EM, Schwahn B, Tokatli A, Dursun A, Coskun T, Chalmers RA, Koeller DM, Zschocke J, Christensen E, Burgard P, Hoffmann GF: Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr Res. 2006, 59: 840-847. 10.1203\/01.pdr.0000219387.79887.86.","journal-title":"Pediatr Res"},{"key":"308_CR20","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1203\/PDR.0b013e318137a124","volume":"62","author":"S K\u00f6lker","year":"2007","unstructured":"K\u00f6lker S, Garbade SF, Boy N, Maier EM, Meissner T, M\u00fchlhausen C, Hennermann JB, L\u00fccke T, H\u00e4berle J, Baumk\u00f6tter J, Haller W, Muller E, Zschocke J, Burgard P, Hoffmann GF: Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany. Pediatr Res. 2007, 62: 357-363. 10.1203\/PDR.0b013e318137a124.","journal-title":"Pediatr Res"},{"key":"308_CR21","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.ymgme.2008.10.003","volume":"96","author":"RC Griggs","year":"2009","unstructured":"Griggs RC, Batshaw M, Dunkle M, Gopal-Srivastava R, Kaye E, Krischer J, Nguyen T, Paulus K, Merkel PA, Rare Diseases Clinical Research Network: Clinical research for rare disease: opportunities, challenges, and solutions. Mol Genet Metab. 2009, 96: 20-26. 10.1016\/j.ymgme.2008.10.003.","journal-title":"Mol Genet Metab"},{"key":"308_CR22","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s10545-008-0843-8","volume":"31","author":"B Wilcken","year":"2008","unstructured":"Wilcken B: The consequences of extended newborn screening programmes: Do we know who needs treatment?. J Inherit Metab Dis. 2008, 31: 173-177. 10.1007\/s10545-008-0843-8.","journal-title":"J Inherit Metab Dis"},{"key":"308_CR23","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.ymgme.2008.09.005","volume":"95","author":"C Ficicioglu","year":"2008","unstructured":"Ficicioglu C, Thomas N, Yager C, Gallagher PR, Hussa C, Mattie A, Day-Salvatore DL, Forbes BJ: Duarte (DG) galactosemia: a pilot study of biochemical and neurodevelopmental assessment in children detected by newborn screening. Mol Genet Metab. 2008, 95: 206-212. 10.1016\/j.ymgme.2008.09.005.","journal-title":"Mol Genet Metab"},{"key":"308_CR24","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1097\/GIM.0b013e3181d28eb1","volume":"12","author":"JM Perrin","year":"2010","unstructured":"Perrin JM, Knapp AA, Browning MF, Comeau AM, Green NS, Lipstein EA, Metterville DR, Prosser L, Queally D, Kemper AR: An evidence development process for newborn screening. Genet Med. 2010, 12: 131-134. 10.1097\/GIM.0b013e3181d28eb1.","journal-title":"Genet Med"},{"key":"308_CR25","volume-title":"EAHC\/2009\/Health\/09","author":"Evaluation of population newborn screening practices for rare disorders in Member States of the European Union, The tender No.","year":"2011","unstructured":"Evaluation of population newborn screening practices for rare disorders in Member States of the European Union, The tender No. EAHC\/2009\/Health\/09 (Accessed May 18, 2011, at http:\/\/www.iss.it\/cnmr\/prog\/cont.php?;id=1621&lang=1&tipo=64)."},{"key":"308_CR26","first-page":"Suppl 2: S205","volume":"30","author":"B Wilcken","year":"2010","unstructured":"Wilcken B: Expanded newborn screening: reducing harm, assessing benefit. J Inherit Metab Dis. 2010, 30: Suppl 2: S205-S210.","journal-title":"J Inherit Metab Dis"},{"key":"308_CR27","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1007\/s10545-007-0553-7","volume":"30","author":"M Lindner","year":"2007","unstructured":"Lindner M, Abdoh G, Fang-Hoffmann J, Shabeck N, Al-Sayrafi M, Al-Janahi M, Ho S, Abdelrahman MO, Ben-Omran T, Bener A, Schulze A, Al-Rifai H, Al-Thani G, Hoffmann GF: Implementation of extended neonatal screening and a metabolic unit in the State of Qatar: developing and optimizing strategies in cooperation with the Neonatal Screening Center in Heidelberg. J Inherit Metab Dis. 2007, 30: 522-529. 10.1007\/s10545-007-0553-7.","journal-title":"J Inherit Metab Dis"},{"key":"308_CR28","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.jpeds.2009.09.054","volume":"156","author":"H Gan-Schreier","year":"2010","unstructured":"Gan-Schreier H, Kebbewar M, Fang-Hoffmann J, Wilrich J, Abdoh G, Ben-Omran T, Shahbek N, Bener A, Al Rifai H, Al Khal AL, Lindner M, Zschocke J, Hoffmann GF: Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards. J Pediatr. 2010, 156: 427-432. 10.1016\/j.jpeds.2009.09.054.","journal-title":"J Pediatr"},{"issue":"Suppl 1","key":"308_CR29","first-page":"3","volume":"30","author":"M Demirkol","year":"2007","unstructured":"Demirkol M, \u00c7elik S, G\u00f6kgay G, \u00d6zer I, Baykal T, Karada\u011f H, K\u00f6se R: Expanded newborn screening experience in Istanbul. J Inherit Metab Dis. 2007, 30 (Suppl 1): 3.","journal-title":"J Inherit Metab Dis"},{"issue":"Suppl 2","key":"308_CR30","doi-asserted-by":"publisher","first-page":"S295","DOI":"10.1007\/s10545-010-9129-z","volume":"30","author":"DM Niu","year":"2010","unstructured":"Niu DM, Chien YH, Chiang CC, Ho HC, Hwu WL, Kao SM, Chiang SH, Kao CH, Liu TT, Chiang H, Hsiao KJ: Nationwide Survey of Extended Newborn Screening by Tandem Mass Spectrometry in Taiwan. J Inherit Metab Dis. 2010, 30 (Suppl 2): S295-S305.","journal-title":"J Inherit Metab Dis"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1750-1172-6-44.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T14:34:23Z","timestamp":1630506863000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/1750-1172-6-44"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,20]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["308"],"URL":"https:\/\/doi.org\/10.1186\/1750-1172-6-44","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,20]]},"assertion":[{"value":"23 February 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2011","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 2011","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"44"}}