Infants suspected to have very-long chain acyl-CoA dehydrogenase deficiency from newborn screening |
| |
| Affiliation: | 1. Pediatrics, University of Washington, Seattle, WA, USA;2. Environmental and Occupational Health, University of Washington, Seattle, WA, USA;3. Pediatrics, Children''s Hospital of Orange County, Orange, CA, USA;4. Genomics Section, Hawai''i Department of Health, Honolulu, HI, USA;5. Pediatrics, University of California San Diego, La Jolla, CA, USA;6. Genetic Disease Screening Program, California Department of Public Health, Richmond, CA, USA;7. Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA;8. Northwest Regional Newborn Screening Program, Oregon State Public Health Laboratory, Hillsboro, OR, USA;9. Office of Newborn Screening, Washington State Department of Health, Shoreline, WA, USA;1. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA;2. Department of Pediatrics, Division of Neonatology and Developmental Biology, Neonatal Research Center at the UCLA Children''s Discovery & Innovation Institute, David Geffen School of Medicine UCLA, Los Angeles, CA, USA;3. Department of Molecular, Cell and Developmental Biology, UCLA, Los Angeles, CA, USA;1. Biochemical Genetics and National Expanded Newborn Screening, Department of Pathology and Laboratory Medicine, KK Women''s and Children''s Hospital, 100 Bukit Timah Road 229899, Singapore;2. Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 11, Singapore 119228;3. Genetics Services, Department of Paediatrics, KK Women''s and Children''s Hospital, 100 Bukit Timah Road 229899, Singapore;4. Department of Paediatrics, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block Level 12, Singapore 119228;5. Department of Neonatology, KK Women''s and Children''s Hospital, 100 Bukit Timah Road 229899, Singapore;6. South Australian Neonatal Screening Centre Directorate of Genetic and Molecular Pathology Women''s and Children''s Hospital Campus, Adelaide SA Pathology, 72 King William Road, North Adelaide, South Australia 5006, Australia;1. Department of Pediatrics, Peking University First Hospital, Beijing 100034, China;2. The Second Affiliated Hospital &Yuying Children''s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China;1. University Medical Centre Ljubljana, University Children''s Hospital, Bohoriceva 20, Ljubljana, Slovenia;2. University of Ljubljana, Faculty of Medicine, Korytkova ulica 2, Ljubljana, Slovenia |
| |
| Abstract: | Very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) is a fatty acid oxidation disorder with widely varying presentations that has presented a significant challenge to newborn screening (NBS). The Western States Regional Genetics Services Collaborative developed a workgroup to study infants with NBS positive for VLCADD. We performed retrospective analysis of newborns with elevated C14:1-acylcarnitine on NBS in California, Oregon, Washington, and Hawai'i including available confirmatory testing and clinical information.Overall, from 2,802,504 children screened, there were 242 cases screen-positive for VLCADD. There were 34 symptomatic true positive cases, 18 asymptomatic true positives, 112 false positives, 55 heterozygotes, 11 lost to follow-up, and 12 other disorders. One in 11,581 newborns had an abnormal NBS for suspected VLCADD. Comparison of analytes and analyte ratios from the NBS demonstrated statistically significant differences between true positive and false positive groups for C14:1, C14, C14:1/C2, and C14:1/C16. The positive predictive value for all true positive cases was 94%, 54%, and 23% when C14:1 was ≥ 2.0 μM, ≥ 1.0 μM, and ≥ 0.7 μM, respectively. Sequential post-analytical analysis could reduce the referral rate in 25.8% of cases.This study is the largest reported follow-up of infants with NBS screen-positive results for suspected VLCADD and demonstrates the necessity of developing comprehensive and consistent long-term follow-up NBS systems. Application of clinical information revealed differences between symptomatic and asymptomatic children with VLCADD. Comparison of NBS analytes and analyte ratios may be valuable in developing more effective diagnostic algorithms. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
