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Hopkins PV, Klug T, Vermette L, Raburn-Miller J, Kiesling J, Rogers S. Incidence of 4 Lysosomal Storage Disorders From 4 Years of Newborn Screening. JAMA Pediatr. 2018;172(7):696–697. doi:10.1001/jamapediatrics.2018.0263
Newborn screening is recognized as a highly effective public health program to detect certain diseases before detrimental long-term health consequences occur. With advances in screening technologies and therapeutic options becoming available, the US Department of Health and Human Services recently added 2 lysosomal storage disorders (LSDs), Pompe disease and mucopolysaccharidosis I (MPS I), to the Recommended Uniform Screening Panel.1 In addition, several states have legislative mandates to screen for other LSDs not on the Recommended Uniform Screening Panel. The Missouri State Public Health Laboratory has used a fluorimetric enzyme activity test on a digital microfluidic platform to screen all samples from newborns that were received since January 11, 2013, for Pompe, MPS I, Gaucher, and Fabry disorders.2 We herein present our findings on incidence rates for these LSDs from 4 years of full-population testing. These results represent, to our knowledge, the longest prospective, unblinded, full-population testing and follow-up for these LSDs in the United States.
Enzyme activity for acid α-glucosidase deficiency (Pompe disease), acid α-galactosidase deficiency (Fabry disease), acid β-glucocerebrosidase deficiency (Gaucher disease), and acid α-l-iduronidase deficiency (MPS I) was measured from dried blood spots using a fluorescence enzyme assay on the digital microfluidic platform (Baebies, Inc) as previously described.2,3 Missouri newborn specimens received for screening from January 11, 2013, through January 10, 2017, were tested; approximately 308 000 newborns were screened. All 4 LSDs were screened simultaneously from a single newborn dried blood spot sample. Samples with positive findings (with mean triplicate screening values breaching referral cutoff limits for 1 of the LSDs) were referred to 1 of 4 state-contracted genetic referral centers for confirmatory testing and follow-up. The Department of Health and Senior Services received approval from the Institutional Review Board Committee after a full review to waive informed parental consent for the LSD implementation. Missouri had a legislative mandate to screen for LSDs and full population screening would be conducted on every infant equally with referral of positive screening results to our contracted genetic referral centers for follow-up confirmatory testing and treatment if needed.
We identified 133 newborns who were confirmed through diagnostic testing results to have 1 of the 4 LSDs (Table), including 32 with Pompe disease (8 infantile and 24 late-onset), 5 with Gaucher disease, 94 with Fabry disease, and 2 with MPS I. An additional 19 infants were confirmed to have genotypes of unknown significance or onset. These infants need continual follow-up to monitor for potential late-onset disorders. The Table also includes the number of newborns identified with pseudodeficiency, as carriers, or with false-positive findings (confirmatory enzyme activity was in the reference range, and no DNA testing was conducted). False-positive rates ([pseudodeficient + carrier + false-positive findings]/total number screened), incidence rates (confirmed disorder/total number screened), and positive predictive values ([confirmed disorders + genotypes of unknown significance]/number with positive screen results) were also calculated.
We report findings from, to our knowledge, the longest unblinded, full-population, prospective study of 4 LSDs in the United States. Although many pilot studies have been performed on blinded samples, Taiwan has the only other collection of newborn screening programs worldwide that has performed population screening for Pompe and Fabry diseases with clinical follow-up for a longer period.4 Incidence rates for Pompe and Fabry diseases in Missouri are similar to those reported in Taiwan, whereas the false-positive rates in Missouri are lower and positive predictive values are higher.4 Incidence rates for Pompe and Fabry disease in Missouri are also higher than recently published rates in Illinois.5 The incidence rates for Gaucher disease and MPS I are similar to those previously reported in other pilot studies.4,5 Rates of pseudodeficiency and genotypes of unknown significance for Pompe disease and MPS I are similar to published rates in Illinois.5 False-positive rates compare well with other newborn screening assays currently performed in Missouri. Missouri State Public Health Laboratory monitors for any false-negative cases, and to date we have had no reports of missed LSD cases. The fluorimetric multiplexed assay streamlines the workflow, makes efficient use of limited newborn screening materials, technical staff, and laboratory space, and allows a same-day turn-around time.
Accepted for Publication: January 24, 2018.
Corresponding Author: Patrick V. Hopkins, BS, Missouri State Public Health Laboratory, 101 N Chestnut St, PO Box 570, Jefferson City, MO 65102 (firstname.lastname@example.org).
Published Online: May 29, 2018. doi:10.1001/jamapediatrics.2018.0263
Author Contributions: Mr Hopkins had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Hopkins, Klug.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Hopkins.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Hopkins, Klug, Kiesling.
Administrative, technical, or material support: Hopkins, Klug, Vermette, Raburn-Miller, Kiesling.
Study supervision: Hopkins, Klug, Rogers.
Conflict of Interest Disclosures: None reported.
Additional Contributions: The Missouri Lysosomal Storage Disease Task Force provided guidance throughout the entire study process. The Missouri Genetic Referral Centers managed referred patients and acquired confirmatory data.