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Retrospective Review of Positive Newborn Screening Results for Isovaleric Acidemia and Development of a Strategy to Improve the Efficacy of Newborn Screening in the UK

Lookup NU author(s): Dr Mark Anderson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2024 by the authors.Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

Publication metadata

Author(s): Carling RS, Hedgethorne K, Chakrapani A, Hall PL, Flynn N, Greenfield T, Moat SJ, Ssali J, Shakespeare L, Taj N, Wu THY, Anderson M, Ghosh A, Lemonde H, Pierre G, Sharrard M, Sreekantam S, Bonham JR

Publication type: Article

Publication status: Published

Journal: International Journal of Neonatal Screening

Year: 2024

Volume: 10

Issue: 1

Print publication date: 01/03/2024

Online publication date: 13/03/2024

Acceptance date: 04/03/2024

Date deposited: 10/04/2024

ISSN (electronic): 2409-515X

Publisher: Multidisciplinary Digital Publishing Institute (MDPI)

URL: https://doi.org/10.3390/ijns10010024

DOI: 10.3390/ijns10010024

Data Access Statement: The data that support the findings of this study are available upon request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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