Abstract
There have been few reports of cases missed by expanded newborn screening. Tandem mass spectrometry was introduced in New South Wales, Australia in 1998 to screen for selected disorders of amino acid, organic acid and fatty acid metabolism. Of 1,500,000 babies screened by 2012, 1:2700 were diagnosed with a target disorder. Fifteen affected babies were missed by testing, and presented clinically or in family studies. In three cases (cobalamin C defect, very-long-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type 1), this led to modification of analyte cut-off values or protocols during the first 3 years. Two patients with intermittent MSUD, two with β-ketothiolase deficiency, two with citrin deficiency, two siblings with arginosuccinic aciduria, two siblings with homocystinuria, and one with cobalamin C defect had analyte values and ratios below the action limits which could not have been detected without unacceptable false-positive rates. A laboratory interpretation error led to missing one case of cobalamin C defect. Reference ranges, regularly reviewed, were not altered. For citrin deficiency, while relevant metabolites are detectable by tandem mass spectrometry, our cut-off values do not specifically screen for that disorder. Most of the missed cases are doing well and with no acute presentations although eight of 15 are likely to have been somewhat adversely affected by a late diagnosis. Analyte ratio and cut-off value optimisations are important, but for some disorders occasional missed cases may have to be tolerated to maintain an acceptable specificity, and avoid harm from screening.
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References
Bhattarcharya K, Khalili V, Wiley V, Carpenter K, Wilcken B (2006) Newborn screening may fail to identify intermediate forms of maple syrup urine disease. J Inherit Metab Dis 29:586
Carpenter KH, Wiley V (2002) Application of tandem mass spectrometry to biochemical genetics and newborn screening. Clin Chim Acta 322:1–10
Couce ML, Castineiras D, Boveda MD et al (2011) Evaluation and long term follow up of infants with inborn errors of metabolism identified in an expanded screening programme. Mol Gen Metab 104:470–475
Feuchtbaum L, Lorey F, Faulkner L et al (2006) California’s experience implementing a pilot newborn supplemental screening program using tandem mass spectrometry. Pediatrics 117:s261–s269
Frazier DM, Millington DS, Mc Candless SE et al (2006) The tandem mass spectrometry experience in North Carolina:1997–2005. J Inherit Metab Dis 29:76–85
Gizicki R, Robert MC, Gomez-Lopez L et al (2014) Long-term visual outcome of methylmalonic aciduria and homocystinuria, cobalamin C type. Ophthalmology 121(1):381–386
Heringer J, Boy SP, Ensenauer R et al (2010) Use of guidelines improves the neurological outcomes in glutaric aciduria type 1. Ann Neurol Nov 68(5):743–752
Kasper DC, Ratschmann R, Metz TF et al (2010) The national Austrian newborn screening program - 8 years experience with mass spectrometry. past, present, and future goals. Wien Klin Wochenschr 122(21-22):607–613
la Marca G, Malvagia S, Casetta B, Pasquini E, Donati MA, Zammarchi E (2008) Progress in expanded newborn screening for metabolic conditions by LC-MS/MS in Tuscany: update on methods to reduce false tests. J Inherit Metab Dis 31(Suppl 2):S395–S404
Linder M, Gramer G, Haege G et al (2011) Efficacy and outcome of expanded newborn screening for metabolic diseases-report of ten years from South-West Germany. Orphanet J Rare Dis 6:44–49
Loukas YL, Soumelas GS, Dotsikas Y et al (2010) Expanded newborn screening in Greece: 30 months of experience. J Inherit Metab Dis 33(Suppl 3):S341–S348
Lund AM, Hougaard DM, Simonsen H et al (2012) Biochemical screening of 504, 049 newborns in Denmark, the Faroe Islands and Greenland- experience and development of a routine program for expanded newborn screening. Mol Gen Metab 107:281–293
Marsden D (2003) Expanded newborn screening by tandem mass spectrometry: the Massachusetts and New England experience. Southeast Asian J Trop Med Public Health 34(Suppl 3):111–114
McHugh D, Cameron CA, Abdenur JE et al (2011) Clinical validation of cut-off target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. Genet Med 13:230–254
Niu DM, Chien YH, Chiang CC et al (2010) Nationwide survey of extended newborn screening by tandem mass spectrometry in Taiwan. J Inherit Metab Dis 33(Suppl 2):S295–S305
Schulze A, Lindner M, Kohlmüller D, Olgemöller K, Mayatepek E, Hoffmann GF (2003) Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications. Pediatrics 111:1399–1406
Shigematsu Y, Hirano S, Hata I et al (2002) Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan. J Chromatogr B Analy Technol Biomed Life Sci 25(776):39–48
Vilarinho L, Rocha H, Sousa C et al (2010) Four years of expanded newborn screening in Portugal with tandem mass spectrometry. J Inherit Metab Dis 33(Suppl 3):S133–S138
Wilcken B, Wiley V (2008) Newborn screening. Pathology 40:104–115
Wilcken B, Wiley V, Hammond J, Carpenter K (2003) Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med 348:2304–2312
Wilcken B, Haas M, Joy P et al (2007) Outcome of neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency in Australia: a cohort study. Lancet. 2007 6;369 (9555):37–42.
Wilcken B, Haas M, Joy P et al (2009) Expanded newborn screening: outcome in screened and unscreened patients at age 6 years. Pediatrics 124(2):e241–e248
Wiley V, Carpenter K, Bayliss U, Wilcken B (2003) Newborn screening- is it really that simple? Southeast Asian J Trop Med Public Health 34(Suppl 3):107–110
Yoon HR, Lee KR, Kang S, et al (2005) Screening of newborns and high-risk group of children for inborn metabolic disorders using tandem mass spectrometry in South Korea: a three-year report. Clin Chim Acta 3542:167–180
Zytkovicz TH, Fitzgerald EF, Marsden D et al (2001) Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England newborn screening program. Clin Chem 47:1945–1955
Acknowledgments
This study was carried out as part of an audit of the NSW Newborn Screening Programme. We are grateful to the clinicians associated with diagnosis and management of the cases – Dr J Christodoulou, Dr C Ellaway, Dr ML Freckman, Dr E Kirk, Dr M Lipke and Dr D Mowat
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The study was carried out as an audit of the newborn screening programme. There was no funding required or received.
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Communicated by: Rodney Pollitt
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Estrella, J., Wilcken, B., Carpenter, K. et al. Expanded newborn screening in New South Wales: missed cases. J Inherit Metab Dis 37, 881–887 (2014). https://doi.org/10.1007/s10545-014-9727-2
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DOI: https://doi.org/10.1007/s10545-014-9727-2