Acquired vitamin B12 (vB12) deficiency (vB12D) of newborns is relatively frequent as compared with the incidence of inherited diseases included in newborn screening (NBS) of different countries across the globe. Infants may present signs of vB12D before 6 months of age with anemia and/or neurologic symptoms when not diagnosed in asymptomatic state. The possibility of identifying vitamin deficient mothers after their pregnancy during the breastfeeding period could be an additional benefit of the newborn screening. Vitamin supplementation is widely available and easy to administer. However, in many laboratories, vB12D is not included in the national screening program. Optimized screening requires either second-tier testing or analysis of new urine and blood samples combined with multiple clinical and laboratory follow ups. Our scope was to review the physiologic fate of vB12 and the pathobiochemical consequences of vB12D in the human body. Particular emphasis was put on the latest approaches for diagnosis and treatment of vB12D in NBS.

The growing need to identify spinal muscular atrophy (SMA) patients as early as possible has shifted attention to newborn screening (NBS). The aim of the present study was to evaluate the possibility of including the SMA-NBS in the Hungarian screening panel. As the first step, a government-funded pilot program started in November 2022 and continued until the end of 2023. Evaluation of the first 14 months was followed by the decision to lengthen the program until the end of 2024, which was further supported by the needs of society. Screening tests were performed in both Hungarian national screening laboratories uniformly using the combined EONIS SCID-SMA real-time PCR assay kit by Revvity, for the newborns whose parents gave written consent for the analysis. Altogether, 155,985 newborns were screened during the 26 months of the program, which was 87% of all newborns involved in the national neonatal screens of the same period. All 19 newborns identified on the screen were diagnosed with SMA, confirmed by a multiplex ligation-dependent probe amplification assay (MLPA). The favorable results of the pilot study support the inclusion of the SMA in the national screening panel at the earliest possible date.

The aim of this study is to evaluate the strategy of the cystic fibrosis newborn screening (CFNBS) programme in Hungary based on the results of the first year of screening. A combined immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) CFNBS protocol (IRT/IRT×PAP/IRT) was applied with an IRT-dependent safety net (SN). Out of 88,400 newborns, 256 were tested screen-positive. Fourteen cystic fibrosis (CF) and two cystic fibrosis-positive inconclusive diagnosis (CFSPID) cases were confirmed from the screen-positive cases, and two false-negative cases were diagnosed later. Based on the obtained results, a sensitivity of 88% and a positive predictive value (PPV) of 5.9% were calculated. Following the recognition of false-negative cases, the calculation method of the age-dependent cut-off was changed. In purely biochemical CFNBS protocols, a small protocol change, even after a short period, can have a significant positive impact on the performance. CFNBS should be monitored continuously in order to fine-tune the screening strategy and define the best local practices.

Sodium-glucose cotransporter 2 inhibitors, such as empagliflozin (EMPA), have been increasingly investigated for their potential neuroprotective properties, but their overall metabolic impact in Parkinson’s disease (PD) remains incompletely understood. Using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, we investigated the effect of EMPA on tryptophan (TRP) metabolism, neurotransmitter levels and antioxidant markers in the striatum. Targeted ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) was used for metabolite quantification. Pairwise group differences were assessed using Welch’s two-sample t -test, with false discovery rate correction, and multivariate analyses were applied for exploratory pattern recognition. EMPA treatment significantly enhanced the neuroprotective arm of the kynurenine pathway (KP), increasing kynurenic acid (KA), anthranilic acid (AA), xanthurenic acid (XA) and the corresponding enzymatic activity ratios in MPTP-induced PD animals. The selective elevation of the KA/TRP ratio without a corresponding change in KYN/TRP suggests that EMPA acts specifically on the KAT-mediated neuroprotective branch, potentially through restoration of astrocytic redox state in the striatum, rather than through generalized modulation of IDO/TDO-driven TRP catabolism. In Sirtuin3 knock-out (S3KO) mice, EMPA reduced 3-hydroxykynurenine (3OHK) levels and the Oxidative Stress Index (3OHK/(KA + AA + XA)), and improved glutathione redox status, as reflected by reduced GSSG levels and an improved GSH/GSSG ratio. These results demonstrate that EMPA exerts significant neurometabolic effects in a mouse model of PD, shifting KP flux towards neuroprotective metabolites and improving redox homeostasis—particularly in the context of mitochondrial dysfunction modelled by Sirtuin3 deficiency. Future studies extending these findings to additional experimental models and clinical settings will be essential to fully elucidate the translational potential of EMPA in neurodegeneration.

Newborn screening (NBS), one of the most important public health care prevention programs, aims at the early identification of asymptomatic newborns at increased risk for inherited disorders, facilitating timely intervention to reduce morbidity and mortality. NBS in Hungary is celebrating the 50th anniversary of the nationwide implementation of screening for phenylketonuria and galactosemia, as well as the 40th anniversary of congenital hypothyroidism screening. The present paper reviews the early years, the present situation, and future perspectives for the Hungarian NBS program. Today, screening for 27 disorders (opt-out) plus spinal muscular atrophy (opt-in) is supported by two centralized and well-equipped laboratories in Budapest and Szeged, in-depth laboratory knowledge, a robust follow-up system, and governmental financial support. Since 1975, 3,289 patients have been confirmed with a screened condition from over 5.6 million newborns screened. The 50-year anniversary of the Hungarian NBS program highlights the dedication of both past and current professionals, ongoing advancements in analytical methods and laboratory information management systems, and alignment with international standards. The equitable provision of screening services continues to be prioritized for all newborns nationwide and within the broader Euro-regional context.