1. Newborn screening for rare diseases : expanding the paradigm in the genomic eraUrh Grošelj, 2026, review article Abstract: Background: Newborn screening (NBS) has long been a cornerstone of public health, initially designed to detect a few congenital disorders such as phenylketonuria and congenital hypothyroidism. This early intervention prevents irreversible health consequences. With the advent of genomic technologies, NBS programs are expanding to include a broader range of rare diseases (RDs), offering new opportunities and challenges in clinical implementation, ethics, and health system readiness. Content: This mini-review traces the evolution of NBS from biochemical assays to next-generation sequencing (NGS) and whole-exome sequencing (WES). It highlights complexities in integrating RDs into NBS panels, including condition selection, test validation, confirmatory pipelines, and the need for robust follow-up. Ethical tensions between public health goals – focused on population benefit – and the personalized medicine paradigm are discussed, along with the importance of international harmonization to ensure equitable access. Summary: Expanding NBS to include RDs can transform early diagnosis, reduce diagnostic delays, and enable timely interventions that improve outcomes. Successful genomic NBS (gNBS) integration requires clear, evidence-based inclusion criteria, validated diagnostics, and sustainable follow-up systems. Outlook: Rapidly evolving genomic tools will reshape NBS, demanding agile policies, secure data infrastructures, and careful attention to consent, privacy, and equity. International collaboration and stakeholder engagement will be essential to ensure these technologies are implemented ethically and effectively, balancing public health priorities with individualized care.
Keywords: newborn screenin, NBS, genomic NBS, rare diseases, public health, personalized medicine, rare diseases
Published in DiRROS: 18.03.2026; Views: 199; Downloads: 153
 Full text (254,89 KB)
This document has many files! More... |
2. Current status of newborn screening in Southeastern and Central EuropeNika Požun, Daša Perko, Violeta Anastasovska, Tadej Battelino, Ana Drole Torkar, Matej Mlinarič, Žiga Iztok Remec, Barbka Repič-Lampret, Domen Trampuž, Mojca Žerjav-Tanšek, Urh Grošelj, 2026, original scientific article Abstract: Newborn screening (NBS) is a well-established public health program that enables early detection and treatment of rare disorders in newborns, preventing severe complications or death. Despite its recognized importance, the scope and implementation of NBS programs vary across Southeastern (SE) and Central Europe. This study aimed to evaluate the current status of NBS in 16 countries of SE and Central Europe and assess progress since the previous survey in 2021. A structured questionnaire was distributed to national experts between April and December 2025, collecting data on program organization, coverage, diseases included, laboratory methods, confirmatory testing, consent practices, and future expansion plans. All countries reported universal screening for congenital hypothyroidism, except Kosovo, where a national NBS is in the process of being established. Expanded NBS using tandem mass spectrometry was available in Austria, Bulgaria, Croatia, Cyprus, Greece, Hungary, North Macedonia, Romania, and Slovenia. Spinal muscular atrophy screening became universal in Austria, Croatia, Hungary, Serbia, and Slovenia. Most countries reported plans for further expansion, with congenital adrenal hyperplasia, severe combined immunodeficiency, spinal muscular atrophy, and cystic fibrosis being the most frequently targeted conditions. Although notable infrastructural progress has been achieved, financial constraints, lack of staff, and organizational barriers remain key challenges. The study’s assessment of program effectiveness was further limited by the absence of region-wide systems for capturing end-to-end performance indicators, such as the age of the infant at treatment initiation or missed cases. Regional collaboration and adoption of best practices are therefore vital to ensure equitable access and continuous advancement of NBS programs.
Keywords: newborn screening, NBS, Southeastern Europe, Central Europe, neonatal screening, expanded NBS program
Published in DiRROS: 06.03.2026; Views: 306; Downloads: 209
Full text (749,60 KB)
This document has many files! More... |
3. Sudden death of a four-day-old newborn due to mitochondrial trifunctional protein/long-chain 3-hydroxyacyl-coa dehydrogenase deficiencies and a systematic literature review of early deaths of neonates with fatty acid oxidation disordersAna Drole Torkar, Ana Klinc, Žiga Iztok Remec, Branislava Ranković, Klara Bartolj, Sara Bertok, Sara Colja, Vanja Čuk, Maruša Debeljak, Eva Kozjek, Barbka Repič-Lampret, Matej Mlinarič, Tinka Mohar Hajnšek, Daša Perko, Katarina Štajer, Tine Tesovnik, Domen Trampuž, Blanka Ulaga, Jernej Kovač, Tadej Battelino, Mojca Žerjav-Tanšek, Urh Grošelj, 2025, review article Abstract: Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies have been a part of the Slovenian newborn screening (NBS) program since 2018. We describe a case of early lethal presentation of MTPD/LCHADD in a term newborn. The girl was born after an uneventful pregnancy and delivery, and she was discharged home at the age of 3 days, appearing well. At the age of 4 days, she was found without signs of life. Resuscitation was not successful. The NBS test performed using tandem mass spectrometry (MS/MS) showed a positive screen for MTPD/LCHADD. Genetic analysis performed on a dried blood spot (DBS) sample identified two heterozygous variants in the HADHA gene: a nucleotide duplication introducing a premature termination codon (p.Arg205Ter) and a nucleotide substitution (p.Glu510Gln). Post-mortem studies showed massive macro-vesicular fat accumulation in the liver and, to a smaller extent, in the heart, consistent with MTPD/LCHADD. A neonatal acute cardiac presentation resulting in demise was suspected. We conducted a systematic literature review of early neonatal deaths within 14 days postpartum attributed to confirmed fatty acid oxidation disorders (FAODs), which are estimated to account for 5% of sudden infant deaths. We discuss the pitfalls of the NBS for MTPD/LCHADD.
Keywords: FAOD, LCHAD deficiency, LCHADD, MTP deficiency, MTPD, NBS, fatty acid oxidation disorder, newborn, newborn screening, sudden infant death
Published in DiRROS: 11.12.2025; Views: 400; Downloads: 284
Full text (839,28 KB)
This document has many files! More... |
