Journal Article

Expanded newborn screening in New South Wales: missed cases

Tchan, Michel, Wiley, Veronica, Estrella, Jane, Wilcken, Bridget, Carpenter, Kevin, Bhattacharya, Kaustuv

2014

Overview

There have been few reports of cases missed by expanded newborn screening. Tandem mass spectrometry was introduced in New South Wales, Australia in 1998 to screen for selected disorders of amino acid, organic acid and fatty acid metabolism. Of 1,500,000 babies screened by 2012, 1:2700 were diagnosed with a target disorder. Fifteen affected babies were missed by testing, and presented clinically or in family studies. In three cases (cobalamin C defect, very-long-chain acyl-CoA dehydrogenase deficiency and glutaric aciduria type 1), this led to modification of analyte cut-off values or protocols during the first 3 years. Two patients with intermittent MSUD, two with β-ketothiolase deficiency, two with citrin deficiency, two siblings with arginosuccinic aciduria, two siblings with homocystinuria, and one with cobalamin C defect had analyte values and ratios below the action limits which could not have been detected without unacceptable false-positive rates. A laboratory interpretation error led to missing one case of cobalamin C defect. Reference ranges, regularly reviewed, were not altered. For citrin deficiency, while relevant metabolites are detectable by tandem mass spectrometry, our cut-off values do not specifically screen for that disorder. Most of the missed cases are doing well and with no acute presentations although eight of 15 are likely to have been somewhat adversely affected by a late diagnosis. Analyte ratio and cut-off value optimisations are important, but for some disorders occasional missed cases may have to be tolerated to maintain an acceptable specificity, and avoid harm from screening.

• Publisher: Springer Netherlands,Springer,Blackwell Publishing Ltd
• Subject: Acetyl-CoA C-Acyltransferase - deficiency / Acyl-CoA Dehydrogenase, Long-Chain - deficiency / Amino Acid Metabolism, Inborn Errors - diagnosis / Amino Acids - blood / Biochemistry / Biological and medical sciences / Brain Diseases, Metabolic - diagnosis / Child, Preschool / Diagnostic Errors / Glutaryl-CoA Dehydrogenase - deficiency / Human Genetics / Humans / Infant / Infant, Newborn / Internal Medicine / Lipid Metabolism, Inborn Errors - diagnosis / Medical genetics / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Mitochondrial Diseases - diagnosis / Muscular Diseases - diagnosis / Neonatal Screening - methods / New South Wales / Original Article / Pediatrics / Prevention and actions / Public health. Hygiene / Public health. Hygiene-occupational medicine / Reference Values / Sensitivity and Specificity / Tandem Mass Spectrometry - methods