introduction of a novel cut-off in newborn screening of galactosemia; a cohort study

Background: the current newborn screening for classic galactosemia (cg) presents significant challenges, including a low positive rate and a high false-positive rate.objectives: in this study, we aimed to establish new cut-off values (covs) for cg screening and introduce a novel approach.methods: total galactose (tgal: the sum of galactose (gal) and galactose-1-phosphate (g-1-p)) levels of all newborns born in fars, iran, from august 2006 to december 2020, were reviewed to establish cut-off ranges. a receiver operating characteristic (roc) curve analysis was performed to define an optimal cov.results: out of 1,187,436 newborns, 4,893 (0.41%) were recalled for further evaluation due to an initial tgal ≥ 4 mg/dl from a positive screening test, with 160 (3.26%) confirmed to have cg. in the initial negative screening results, nine infants were missed as false negatives. an area under the curve of 0.868 suggested that tgal is a reliable indicator for distinguishing galactosemia from normal subjects. receiver operating characteristic curve analysis indicated that a cut-off value (cov) of 5.2 mg/dl provided a sensitivity and specificity of 80.0% and 81.3%, respectively, making it an optimal conservative value for deciding on further recall in the iranian setting. additionally, a cov of 7.35 mg/dl demonstrated a sensitivity of 71.3% and specificity of 95.7%, making it a suitable cut-off for immediate referral.conclusions: we proposed a novel protocol for newborn screening in iran, establishing a tgal level of 5.2 mg/dl as a conservative cut-off for cg screening, showing excellent sensitivity while ensuring specificity for recalling suspicious cases. furthermore, a cut-off of 7.35 mg/dl was identified for prompt consideration of urgent treatment.