Min-Ju Chan1, Hsuan-Chieh Liao1, Michael H Gelb2, Chih-Kuang Chuang3, Mei-Ying Liu1, Hsiao-Jan Chen1, Shu-Min Kao1, Hsiang-Yu Lin4, You-Hsin Huang5, Arun Babu Kumar6, Naveen Kumar Chennamaneni6, Nagendar Pendem6, Shuan-Pei Lin3, Chuan-Chi Chiang7. 1. Neonatal Screening Center, The Chinese Foundation of Health, Taipei, Taiwan. 2. Department of Chemistry, University of Washington, Seattle, WA; Department of Biochemistry, University of Washington, Seattle, WA. 3. Division of Genetics and Metabolism, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan. 4. Division of Genetics and Metabolism, Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Nursing and Management, Mackay Junior College of Medicine, Taipei, Taiwan. 5. Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan. 6. Department of Chemistry, University of Washington, Seattle, WA. 7. Neonatal Screening Center, The Chinese Foundation of Health, Taipei, Taiwan. Electronic address: ccchiang@cfoh.org.tw.
Abstract
OBJECTIVE: To evaluate the initial cutoff values, rates of screen positives, and genotypes for the large-scale newborn screening program for multiple mucopolysaccharidoses (MPS) in Taiwan. STUDY DESIGN: More than 100 000 dried blood spots were collected consecutively as part of the national Taiwan newborn screening programs. Enzyme activities were measured by tandem mass spectrometry from dried blood spot punches. Genotypes were obtained when a second newborn screening specimen again had a decreased enzyme activity. Additional clinical evaluation was then initiated based on enzyme activity and/or genotype. RESULTS: Molecular genetic analysis for cases with low enzyme activity revealed 5 newborns with pathogenic alpha-L-iduronidase mutations, 3 newborns with pathogenic iduronate-2-sulfatase mutations, and 1 newborn was a carrier of an arylsulfatase B mutation. Several variants of unknown pathogenic significance were also identified, most likely causing pseudodeficiency. CONCLUSIONS: The highly robust tandem mass spectrometry-based enzyme assays for MPS-I, MPS-II, and MPS-VI allow for high-throughput newborn screening for these lysosomal storage disorders. Optimized cutoff values combined with second tier testing could largely eliminate false-positive results. Accordingly, newborn screening for these lysosomal storage disorders is possible.
OBJECTIVE: To evaluate the initial cutoff values, rates of screen positives, and genotypes for the large-scale newborn screening program for multiple mucopolysaccharidoses (MPS) in Taiwan. STUDY DESIGN: More than 100 000 dried blood spots were collected consecutively as part of the national Taiwan newborn screening programs. Enzyme activities were measured by tandem mass spectrometry from dried blood spot punches. Genotypes were obtained when a second newborn screening specimen again had a decreased enzyme activity. Additional clinical evaluation was then initiated based on enzyme activity and/or genotype. RESULTS: Molecular genetic analysis for cases with low enzyme activity revealed 5 newborns with pathogenic alpha-L-iduronidase mutations, 3 newborns with pathogenic iduronate-2-sulfatase mutations, and 1 newborn was a carrier of an arylsulfatase B mutation. Several variants of unknown pathogenic significance were also identified, most likely causing pseudodeficiency. CONCLUSIONS: The highly robust tandem mass spectrometry-based enzyme assays for MPS-I, MPS-II, and MPS-VI allow for high-throughput newborn screening for these lysosomal storage disorders. Optimized cutoff values combined with second tier testing could largely eliminate false-positive results. Accordingly, newborn screening for these lysosomal storage disorders is possible.
Authors: Yang Liu; Fan Yi; Arun Babu Kumar; Naveen Kumar Chennamaneni; Xinying Hong; C Ronald Scott; Michael H Gelb; Frantisek Turecek Journal: Clin Chem Date: 2017-04-20 Impact factor: 8.327
Authors: Nouriya Abbas Al-Sannaa; Hind Yousif Al-Abdulwahed; Sami Ibrahim Al-Majed; Issam Hassan Bouholaigah Journal: J Community Genet Date: 2017-09-15
Authors: Dawn S Peck; Jean M Lacey; Amy L White; Gisele Pino; April L Studinski; Rachel Fisher; Ayesha Ahmad; Linda Spencer; Sarah Viall; Natalie Shallow; Amy Siemon; J Austin Hamm; Brianna K Murray; Kelly L Jones; Dimitar Gavrilov; Devin Oglesbee; Kimiyo Raymond; Dietrich Matern; Piero Rinaldo; Silvia Tortorelli Journal: Int J Neonatal Screen Date: 2020-02-07