Hsuan-Chieh Liao1,2, Min-Ju Chan3, Chia-Feng Yang4,5, Chuan-Chi Chiang3, Dau-Ming Niu2,4, Chun-Kai Huang4, Michael H Gelb6. 1. The Chinese Foundation of Health, Neonatal Screening Center, Taipei, Taiwan; liaojoyce@cfoh.org.tw gelb@chem.washington.edu. 2. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 3. The Chinese Foundation of Health, Neonatal Screening Center, Taipei, Taiwan. 4. Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan. 5. Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan. 6. Departments of Chemistry and Biochemistry, University of Washington, Seattle, WA. liaojoyce@cfoh.org.tw gelb@chem.washington.edu.
Abstract
BACKGROUND: Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up. METHODS: We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively large analytical range compared to the fluorimetric assay with 4-methylumbelliferyl-α-glucoside. DBS from newborns confirmed to have infantile-onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12) and those from patients bearing pseudodeficiency alleles with or without Pompe mutations, or Pompe disease carriers (n = 230) were studied. RESULTS: With use of the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the Pompe disease carriers were well separated from the IOPD and LOPD newborns. The fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD group. CONCLUSIONS: The relatively large analytical range MS/MS GAA assay but not the fluorimetric assay in DBS provides a robust approach to reduce the number of referrals and should dramatically facilitate newborn screening of Pompe disease.
BACKGROUND: Deficiency of the lysosomal enzyme acid α-glucosidase (GAA) causes Pompe disease. Newborn screening for Pompe disease is ongoing, and improved methods for distinguishing affected patients from those with pseudodeficiency, especially in the Asian population, would substantially reduce the number of patient referrals for clinical follow-up. METHODS: We measured the enzymatic activity of GAA in dried blood spots on newborn screening cards (DBS) using a tandem mass spectrometry (MS/MS) assay. The assay displayed a relatively large analytical range compared to the fluorimetric assay with 4-methylumbelliferyl-α-glucoside. DBS from newborns confirmed to have infantile-onset Pompe disease (IOPD, n = 11) or late-onset Pompe disease (LOPD) (n = 12) and those from patients bearing pseudodeficiency alleles with or without Pompe mutations, or Pompe disease carriers (n = 230) were studied. RESULTS: With use of the MS/MS GAA assay in DBS, 96% of the pseudodeficiency newborns and all of the Pompe disease carriers were well separated from the IOPD and LOPD newborns. The fluorimetric assay separated <10% of the pseudodeficiencies from the IOPD/LOPD group. CONCLUSIONS: The relatively large analytical range MS/MS GAA assay but not the fluorimetric assay in DBS provides a robust approach to reduce the number of referrals and should dramatically facilitate newborn screening of Pompe disease.
Authors: B Winchester; D Bali; O A Bodamer; C Caillaud; E Christensen; A Cooper; E Cupler; M Deschauer; K Fumić; M Jackson; P Kishnani; L Lacerda; J Ledvinová; A Lugowska; Z Lukacs; I Maire; H Mandel; E Mengel; W Müller-Felber; M Piraud; A Reuser; T Rupar; I Sinigerska; M Szlago; F Verheijen; O P van Diggelen; B Wuyts; E Zakharova; J Keutzer Journal: Mol Genet Metab Date: 2007-12-19 Impact factor: 4.797
Authors: Angéla Dajnoki; György Fekete; Joan Keutzer; Joseph J Orsini; Victor R De Jesus; Yin-Hsiu Chien; Wuh-Liang Hwu; Zoltan Lukacs; Adolf Mühl; X Kate Zhang; Olaf Bodamer Journal: Clin Chim Acta Date: 2010-03-22 Impact factor: 3.786
Authors: X Kate Zhang; Carole S Elbin; Wei-Lien Chuang; Samantha K Cooper; Carla A Marashio; Christa Beauregard; Joan M Keutzer Journal: Clin Chem Date: 2008-08-21 Impact factor: 8.327
Authors: C Ronald Scott; Susan Elliott; Norman Buroker; Lauren I Thomas; Joan Keutzer; Michael Glass; Michael H Gelb; Frantisek Turecek Journal: J Pediatr Date: 2013-03-01 Impact factor: 4.406
Authors: Susan Elliott; Norman Buroker; Jason J Cournoyer; Anna M Potier; Joseph D Trometer; Carole Elbin; Mack J Schermer; Jaana Kantola; Aaron Boyce; Frantisek Turecek; Michael H Gelb; C Ronald Scott Journal: Mol Genet Metab Date: 2016-05-20 Impact factor: 4.797
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: Conlan Kreher; Jacob Favret; Nadav I Weinstock; Malabika Maulik; Xinying Hong; Michael H Gelb; Lawrence Wrabetz; M Laura Feltri; Daesung Shin Journal: PLoS Biol Date: 2022-07-05 Impact factor: 9.593
Authors: Pavlina Wolf; Roy N Alcalay; Christopher Liong; Emmaline Cullen; Michael W Pauciulo; William C Nichols; Ziv Gan-Or; Wendy K Chung; Tina Faulkner; Christopher Bentis; Robert J Pomponio; Xiwen Ma; X Kate Zhang; Joan M Keutzer; Petra Oliva Journal: Mol Genet Metab Date: 2017-10-23 Impact factor: 4.797
Authors: Anirudh J Ullal; Hong Pham; Rajendra Singh; Peter Ross; Carrie A Graham; Scott M Norton; Miriam H Nuffer; Debbie S Burns; Allen E Eckhardt; Maria Escolar; Deeksha Bali; Vamsee K Pamula Journal: Pract Lab Med Date: 2019-10-16