Barbara K Burton1, Joel Charrow2, George E Hoganson3, Darrell Waggoner4, Brad Tinkle5, Stephen R Braddock6, Michael Schneider7, Dorothy K Grange8, Claudia Nash9, Heather Shryock9, Rebecca Barnett9, Rong Shao10, Khaja Basheeruddin10, George Dizikes11. 1. Department of Pediatrics, Division of Genetics, Birth Defects & Metabolism, Ann & Robert H. Lurie Children's Hospital, Feinberg School of Medicine of Northwestern University, Chicago, IL. Electronic address: BBurton@luriechildrens.org. 2. Department of Pediatrics, Division of Genetics, Birth Defects & Metabolism, Ann & Robert H. Lurie Children's Hospital, Feinberg School of Medicine of Northwestern University, Chicago, IL. 3. Department of Pediatrics, Division of Genetics, University of Illinois College of Medicine, Chicago, IL. 4. Department of Pediatric, Department of Human Genetics, University of Chicago, Chicago, IL. 5. Department of Genetics, Division of Clinical Genetics, Advocate Children's Hospital, Park Ridge, IL. 6. Department of Pediatrics, Division of Medical Genetics, Saint Louis University School of Medicine, St. Louis, MO. 7. Department of Pediatrics, Division of Medical Genetics, Carle Clinic, Champaign, IL. 8. Department of Pediatrics, Division of Genetics and Genomic Medicine, Washington University School of Medicine, St. Louis, MO. 9. Genetics Program, Illinois Department of Public Health, Springfield, IL. 10. Newborn Screening Laboratory, Illinois Department of Public Health, Chicago, IL. 11. Newborn Screening Laboratory, Illinois Department of Public Health, Chicago, IL; Division of Laboratory Services, Tennessee Department of Health, Nashville, TN.
Abstract
OBJECTIVES: To assess the outcomes of newborn screening for 5 lysosomal storage disorders (LSDs) in the first cohort of infants tested in the state of Illinois. STUDY DESIGN: Tandem mass spectrometry was used to assay for the 5 LSD-associated enzymes in dried blood spot specimens obtained from 219 973 newborn samples sent to the Newborn Screening Laboratory of the Illinois Department of Public Health in Chicago. RESULTS: The total number of cases with a positive diagnosis and the incidence for each disorder were as follows: Fabry disease, n = 26 (1 in 8454, including the p.A143T variant); Pompe disease, n = 10 (1 in 21 979); Gaucher disease, n = 5 (1 in 43 959); mucopolysaccharidosis (MPS) type 1, n = 1 (1 in 219 793); and Niemann-Pick disease type A/B, n = 2 (1 in 109 897). Twenty-two infants had a positive screen for 1 of the 5 disorders but could not be classified as either affected or unaffected after follow-up testing, including genotyping. Pseudodeficiencies for alpha-L-iduronidase and alpha-glucosidase were detected more often than true deficiencies. CONCLUSIONS: The incidences of Fabry disease and Pompe disease were significantly higher than published estimates, although most cases detected were predicted to be late onset. The incidences of Gaucher disease, MPS I, and Niemann-Pick disease were comparable with previously published estimates. A total of 16 infants could not be positively identified as either affected or unaffected. To validate the true risks and benefits of newborn screening for LSD, long term follow-up in these infants and those detected with later-onset disorders will be essential.
OBJECTIVES: To assess the outcomes of newborn screening for 5 lysosomal storage disorders (LSDs) in the first cohort of infants tested in the state of Illinois. STUDY DESIGN: Tandem mass spectrometry was used to assay for the 5 LSD-associated enzymes in dried blood spot specimens obtained from 219 973 newborn samples sent to the Newborn Screening Laboratory of the Illinois Department of Public Health in Chicago. RESULTS: The total number of cases with a positive diagnosis and the incidence for each disorder were as follows: Fabry disease, n = 26 (1 in 8454, including the p.A143T variant); Pompe disease, n = 10 (1 in 21 979); Gaucher disease, n = 5 (1 in 43 959); mucopolysaccharidosis (MPS) type 1, n = 1 (1 in 219 793); and Niemann-Pick disease type A/B, n = 2 (1 in 109 897). Twenty-two infants had a positive screen for 1 of the 5 disorders but could not be classified as either affected or unaffected after follow-up testing, including genotyping. Pseudodeficiencies for alpha-L-iduronidase and alpha-glucosidase were detected more often than true deficiencies. CONCLUSIONS: The incidences of Fabry disease and Pompe disease were significantly higher than published estimates, although most cases detected were predicted to be late onset. The incidences of Gaucher disease, MPS I, and Niemann-Pick disease were comparable with previously published estimates. A total of 16 infants could not be positively identified as either affected or unaffected. To validate the true risks and benefits of newborn screening for LSD, long term follow-up in these infants and those detected with later-onset disorders will be essential.
Authors: James J Miller; Kazuhiro Aoki; Francie Moehring; Carly A Murphy; Crystal L O'Hara; Michael Tiemeyer; Cheryl L Stucky; Nancy M Dahms Journal: JCI Insight Date: 2018-03-22