Systematic Review and Meta-Analysis on Diagnostic Test of Biomarkers for Classical Galactosaemia

Abstract

Background: Classical galactosaemia (CG) is an autosomal recessive inherited disorder caused by deficiency in galactose-1-phosphate uridyl transferase (GALT) enzyme, resulting in accumulation of galactose and galactose-1-phosphate. The primary aims of this systematic review were to evaluate the analytical and diagnostic test of total galactose (TG) and GALT as clinical biomarkers for CG. Methods: Systematic search strategies were developed based on PRISMA guideline. Selection of relevant manuscripts, risk of bias assessment, and data extraction were performed independently by three investigators. Diagnostic tests of sensitivity and specificity were determined and translated to receiver operating curve (ROC) and area under curve (AUROC) while Fisher’s exact test was performed to analyse the contingency table. Results: Five studies were included in the meta-analysis. Diagnosis of CG was divided based on approach A (TG; 4 studies; n=241,365), approach B (GALT; 2 studies; n=791), approach C (TG as first tier and GALT as second tier; 1 study; n=139) and approach D (GALT as first tier and TG as second tier; 4 studies; n=1,593,586). Mean of sensitivity and specificity for approach A, B, C, and D were 1.000 (95% confidence interval, CI: 0.966-1.000) and 0.918 (95% CI: 0.917-0.919) (p value <0.01); 1.000 (95% CI: 0.701-1.0) and 1.000 (95% CI: 0.995-1.000) (p value <0.01); 1.000 (95% CI: 0.051-1.000) and 0.674 (95% CI: 0.592-0.747) (p value > 0.05); and 1.000 (95% CI: 0.875-1.000) and 0.999 (95% CI: 0.9996-0.9997), respectively. AUROC (standard error) for approach A, B, C, and D were 1.000 (0.000); 0.625 (0.3207); 1.000 (0.000); and 1.000 (0.000), respectively. Conclusion: Approach D show high sensitivity and specificity with low values of CI indicating that the approach is suitable for screening of CG. Thus, it is recommended that clinical laboratory may consider using GALT assay as first tier of screening and TG assay as second tier of screening for CG diagnosis.