Neonatal Screening in Sweden and Disease-Causing Variants in Phenylketonuria, Galactosaemia, and Biotinidase Deficiency

The Swedish neonatal screening program for phenylketonuria (PKU), galactosaemia, and biotinidase deficiency (BD) was effective, with low false positive rates. For galactosaemia, the incidence was 1/100,000, and the program's positive predictive value (PPV) improved by adjusting recall levels to avoid detecting milder variants. Genetic studies identified pathogenic variants in all GALT deficiency patients, with p.Gln188Arg being the most common. Women with GALT deficiency were no longer discouraged from breastfeeding. For PKU, the inclusion of the Phe/Tyr ratio reduced false positives, achieving a PPV of 0.92, and the incidence of milder cases increased due to immigration. BD screening detected mainly profound cases, with p.Thr532Met as the most frequent variant. The program's success suggested potential benefits of including attenuated forms of these disorders in future screenings.