The Risk of Fatty Acid Oxidation Disorders and Organic Acidemias in Children with Normal Newborn Screening.

Wilson C1, Knoll D2, de Hora M3, Kyle C4, Glamuzina E5, Webster D3.

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Abstract

New Zealand has undertaken expanded newborn screening since 2006. During that period there have been no reported cases of fatty acid oxidation disorders or organic acidemias that have been diagnosed clinically that the screening programme missed. However there may have been patients that presented clinically that were not diagnosed correctly or notified.In order to investigate the false-negative screening rate a case-control study was undertaken whereby the clinical coding data and relevant medical records were reviewed for 150 controls and 525 cases. The cases had normal newborn screening but with key analytes and/or ratios just below the notification level for individual disorders and thus in theory were most at risk of having metabolic disease.Two cases had medical histories suggestive of metabolic disease and thus could represent a false-negative screen. One of these had marginally elevated octanoyl carnitine levels and thus possible medium-chain acyl Co-A dehydrogenase deficiency (MCADD) while the other had elevated isovaleryl carnitine and thus may have been a case of isovaleric acidemia (IVA). However, subsequent molecular analysis revealed that the diagnosis of MCADD and IVA was unlikely.Despite relatively high cut-offs the New Zealand Newborn Metabolic Screening Programme does not appear to have missed any confirmed cases of fatty acid oxidation disorders and organic acidemias in its first 8 years of expanded newborn screening. This would suggest a similar low false-negative screening rate in centres with comparable screening protocols and would indicate that the risk of fatty acid oxidation disorders and classical organic acidemias in children who had normal newborn screening is low.