Ulrike Mütze1, Sven F Garbade2, Gwendolyn Gramer2, Martin Lindner3, Peter Freisinger4, Sarah Catharina Grünert5, Julia Hennermann6, Regina Ensenauer7,8, Eva Thimm7, Judith Zirnbauer9, Michael Leichsenring9, Florian Gleich2, Friederike Hörster2, Karina Grohmann-Held2,10, Nikolas Boy2, Junmin Fang-Hoffmann2, Peter Burgard2, Magdalena Walter2, Georg F Hoffmann2, Stefan Kölker2. 1. Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany; ulrike.muetze@med.uni-heidelberg.de. 2. Division of Child Neurology and Metabolic Medicine and Dietmar Hopp Metabolic Center, Center for Child and Adolescent Medicine, University Hospital Heidelberg, Heidelberg, Germany. 3. Division of Pediatric Neurology, University Children's Hospital Frankfurt, Frankfurt, Germany. 4. Children's Hospital Reutlingen, Klinikum am Steinenberg Reutlingen, Reutlingen, Germany. 5. Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center - University of Freiburg, Freiburg, Germany. 6. Villa Metabolica, Center for Pediatric and Adolescent Medicine, University Medical Center Mainz, Mainz, Germany. 7. Department of General Pediatrics, Neonatology, and Pediatric Cardiology, University Children's Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. 8. Institute of Child Nutrition, Max Rubner-Institut, Karlsruhe, Germany. 9. Department of Pediatric and Adolescent Medicine, Medical School, Ulm University, Ulm, Germany; and. 10. Center for Child and Adolescent Medicine, University Hospital Greifswald, Greifswald, Germany.
Abstract
BACKGROUND: Although extended newborn screening (NBS) programs have been introduced more than 20 years ago, their impact on the long-term clinical outcome of individuals with inherited metabolic diseases (IMDs) is still rarely investigated. METHODS: We studied the clinical outcomes of individuals with IMDs identified by NBS between 1999 and 2016 in a prospective multicenter observational study. RESULTS: In total, 306 screened individuals with IMDs (115 with phenylketonuria and 191 with other IMDs with a lifelong risk for metabolic decompensation) were followed for a median time of 6.2 years. Although the risk for metabolic decompensation was disease-specific and NBS could not prevent decompensations in every individual at risk (n = 49), the majority did not develop permanent disease-specific signs (75.9%), showed normal development (95.6%) and normal cognitive outcome (87.7%; mean IQ: 100.4), and mostly attended regular kindergarten (95.2%) and primary school (95.2%). This demonstrates that not only individuals with phenylketonuria, serving as a benchmark, but also those with lifelong risk for metabolic decompensation had a favorable long-term outcome. High NBS process quality is the prerequisite of this favorable outcome. This is supported by 28 individuals presenting with first symptoms at a median age of 3.5 days before NBS results were available, by the absence of neonatal decompensations after the report of NBS results, and by the challenge of keeping relevant process parameters at a constantly high level. CONCLUSIONS: NBS for IMDs, although not completely preventing clinical presentations in all individuals, can be considered a highly successful program of secondary prevention.
BACKGROUND: Although extended newborn screening (NBS) programs have been introduced more than 20 years ago, their impact on the long-term clinical outcome of individuals with inherited metabolic diseases (IMDs) is still rarely investigated. METHODS: We studied the clinical outcomes of individuals with IMDs identified by NBS between 1999 and 2016 in a prospective multicenter observational study. RESULTS: In total, 306 screened individuals with IMDs (115 with phenylketonuria and 191 with other IMDs with a lifelong risk for metabolic decompensation) were followed for a median time of 6.2 years. Although the risk for metabolic decompensation was disease-specific and NBS could not prevent decompensations in every individual at risk (n = 49), the majority did not develop permanent disease-specific signs (75.9%), showed normal development (95.6%) and normal cognitive outcome (87.7%; mean IQ: 100.4), and mostly attended regular kindergarten (95.2%) and primary school (95.2%). This demonstrates that not only individuals with phenylketonuria, serving as a benchmark, but also those with lifelong risk for metabolic decompensation had a favorable long-term outcome. High NBS process quality is the prerequisite of this favorable outcome. This is supported by 28 individuals presenting with first symptoms at a median age of 3.5 days before NBS results were available, by the absence of neonatal decompensations after the report of NBS results, and by the challenge of keeping relevant process parameters at a constantly high level. CONCLUSIONS:NBS for IMDs, although not completely preventing clinical presentations in all individuals, can be considered a highly successful program of secondary prevention.
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