Biochemical and molecular characteristics of patients with organic acidaemias and urea cycle disorders identified through newborn screening

Background: In recent years it has become clear that newborn screening (NBS) programmes using tandem mass spectrometry identify patients with classical inborn errors of metabolism who are asymptomatic. This observation raises issues regarding medicalization of non-diseases, potentially unnecessary treatment and unnecessary anxiety to parents. Aims: This study aims to identify possible markers that may assist in predicting the need for treatment of infants with classical organic acidaemias (OA) and urea cycle disorders (UCD) diagnosed through NBS. Methods: Medical records of all patients with classical OA and UCD detected through the Victorian NBS programme from February 2002 to January 2014, or diagnosed clinically between 1990 and January 2002 were retrospectively reviewed. Results: Neonatal presentation did not always predict the need for on-going strict treatment. Blood concentrations of amino acids and acyl-carnitines and the changes thereof in follow-up samples correlated with severity in citrullinaemia-I, possibly isovaleric acidaemia but not in argininosuccinic aciduria or propionic acidaemia. Some specific mutations correlate with attenuated citrullinaemia-I. Gender may affect clinical outcome in propionic acidaemia. Conclusions: Changes in blood concentration of certain metabolites (amino acids, acyl-camitines) in the first weeks of life may be predictive of the need for treatment in some disorders but not in others. Mutation analysis may be predictive in some disorders but whether or not this should be considered as second-tier testing in NBS should be discussed separately. (C) 2014 Elsevier Inc. All rights reserved.