1 Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet3 unknown4 Institut for Human Genetik5 Klinisk Epidemiologisk Afdeling6 Institut for Klinisk Medicin - Molekylær Medicinsk Forsk.enhed7 Institut for Pædagogisk Psykologi8 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet9 Section of Diagnostic Sciences, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Expanded newborn screening for selected inborn errors of metabolism (IEM) in Denmark, the Faroe Islands and Greenland was introduced in 2002. We now present clinical, biochemical, and statistical results of expanded screening (excluding PKU) of 504,049 newborns during nine years as well as diagnoses and clinical findings in 82,930 unscreened newborns born in the same period. The frequencies of diagnoses made within the panel of disorders screened for are compared with the frequencies of the disorders in the decade preceding expanded newborn screening. The expanded screening was performed as a pilot study during the first seven years, and the experience obtained during these years was used in the development of the routine neonatal screening program introduced in 2009. Methods for screening included tandem mass spectrometry and an assay for determination of biotinidase activity. A total of 310 samples from 504,049 newborns gave positive screening results. Of the 310 results, 114 were true positive, including results from 12 newborns in which the disease in question was subsequently diagnosed in their mothers. Thus, the overall frequency of an IEM in the screening panel was 1:4942 (mothers excluded) or 1:4421 (mothers included). The false positive rate was 0.038% and positive predictive value 37%. Overall specificity was 99.99%. All patients with true positive results were followed in The Center for Inherited Metabolic Disorders in Copenhagen, and the mean follow-up period was 45months (range 2109months). There were no deaths among the 102 children, and 94% had no clinically significant sequelae at last follow-up. Our study confirms the higher frequency of selected IEM after implementation of expanded newborn screening and suggests an improved outcome for several disorders. We argue that newborn screening for these disorders should be standard of care, though unresolved issues remain, e.g. about newborns with a potential for remaining asymptomatic throughout life. Well organized logistics of the screening program from screening laboratory to centralized, clinical management is important.
Molecular Genetics and Metabolism, 2012, Vol 107, Issue 3, p. 281-93