Details

Autor(en) / Beteiligte

• Carling, Rachel S
• Hedgethorne, Katy
• Chakrapani, Anupam
• Hall, Patricia L
• Flynn, Nick
• Greenfield, Toby
• Moat, Stuart J
• Ssali, Joshua
• Shakespeare, Lynette
• Taj, Nazia
• Wu, Teresa H Y
• Anderson, Mark
• Ghosh, Arunabha
• Lemonde, Hugh
• Pierre, Germaine
• Sharrard, Mark
• Sreekantam, Sreevidya
• Bonham, James R

Titel

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

Ist Teil von

• International journal of neonatal screening, 2024-03, Vol.10 (1), p.24

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2024

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 ( = 17), demonstrating a median (range) C5C of 3.0 (1.8-7.1) whilst 'clinically affected' patients ( = 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.