To screen or not to screen G6PD deficiency in gNBS: insights from the BabyDetect pilot and current evidence.

Enzymatic glucose-6-phosphate dehydrogenase deficiency, caused by variants in the G6PD gene, predisposes to neonatal hyperbilirubinaemia and haemolytic crises.

As genomic newborn screening moves toward broader implementation, which conditions to include on first-tier panels remains debated; G6PD deficiency, the most common monogenic disorder worldwide, is inconsistently screened in Europe. Using the Belgian BabyDetect pilot, one of the first European programmes to evaluate genomic and biochemical newborn screening in the same cohort, together with international evidence, the authors assessed its readiness for inclusion. Genomic screening identified 94 newborns carrying pathogenic or likely pathogenic G6PD variants, including 17 not detected by routine biochemical screening. Scored with an adapted NEXUS 2015 semi-quantitative framework, G6PD deficiency reached 17/21, reflecting strong clinical benefit, feasibility and ethical favourability but moderate analytic validity, population impact and evidence strength. The authors conclude that inclusion is justified provided it is paired with confirmatory testing and proportionate paediatric-led follow-up.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The strongest argument is the gap of 17 newborns detected by sequencing and missed by biochemistry: it directly answers the objection of redundancy with existing screening. The downside is acknowledged by the authors, since moderately deficient infants are also detected, with neither penetrance nor follow-up codified, shifting the burden onto paediatric teams. The NEXUS score of 17/21 remains a structured judgement rather than proof of cost-effectiveness: the inclusion decision stays as much political as scientific.

Analysis by Dr Thibaut Benquey