Importance of total galactose and GALT activity for the diagnosis of classical galactosemia

Abstract

Classical galactosaemia (CG) is an autosomal recessive inherited disorder caused by deficiency of galactose-1-phosphate uridyl transferase (GALT) enzyme, resulting in accumulation of galactose and galactose-1-phosphate. Common clinical presentations are jaundice, lethargy, poor feeding, vomiting, septicaemia and may progress to death within a few weeks of life. It is crucial to detect affected newborns before symptoms appear to prevent complications. Therefore, we aimed to determine the analytical and diagnostic efficiency for total galactose measurement and GALT activity quantitation for the diagnosis of CG in Malaysia. A total of 5313 dried blood spots (DBS) from infants aged less than 1 year, including one DBS from a known case of CG were collected from various hospitals in Malaysia. These DBS were subjected to total galactose analysis and GALT activity. The diagnostic performance of total galactose, GALT analysis, and the combination of both methods was calculated and evaluated using receiver operating characteristic (ROC) curve analysis. Total galactose assay as a single screening method for CG showed 0.32% in sensitivity and 98.9 % for specificity. The sensitivity and specificity for the isolated GALT assay were 5.7% and 82.3%, respectively. High sensitivity and specificity of 100% and 99.9% respectively, were achieved when using both methods as a screening method for CG. CG can be confidently diagnosed using both total galactose and GALT assay in DBS.