Personalized Medicine Begins at Birth: Newborn Screening for Spinal Muscular Atrophy in Serbia as a Model of Individualized Care

Abstract

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, with disease-modifying therapies achieving maximal benefit when administered presymptomatically, underscoring the medical, ethical, and public health imperative for newborn screening (NBS). In 2021, Serbia launched its first genetic NBS initiative for SMA, centralized at the Faculty of Biology, University of Belgrade, a center of SMA diagnostics and research since 1997. Over a 17-month pilot study, 12,000 newborns across two maternity hospitals were screened using dried blood spots analyzed by qPCR for SMN1 absence, with confirmatory MLPA testing and SMN2 copy number determination. Following pilot study success, the national SMA screening program began on September 15, 2023, now encompassing 52 public and 6 private maternity hospitals. By September 09, 2025, 119,735 newborns had been screened, identifying 19 infants with SMA; 17 received immediate therapy—6 with 2 SMN2 copies, 7 with 3 copies, and 4 with 4 copies—while 2 infants with 5 SMN2 copies remain under observation. Treated infants remain largely asymptomatic. A multidisciplinary Expert SMA Commission ensures individualized treatment decisions, integrating genetic, clinical, and laboratory data. The program establishes Serbia’s first reliable SMA incidence estimate (1:6,302 births) and demonstrates that presymptomatic diagnosis, structured screening workflows, and personalized therapy can transform SMA from a severe, life-limiting disease into a manageable condition. Serbia’s experience provides a compelling model for integrating precision medicine into national health systems through coordinated collaboration among academia, patient advocacy, industry, and government, illustrating how early genetic diagnosis and tailored interventions can fundamentally change disease trajectories.Spinalna mišićna atrofija (SMA) predstavlja vodeći genetički uzrok smrtnosti odojčadi, pri čemu terapije koje menjaju tok bolesti imaju najveći efekat kada se primene presimptomatski. To naglašava medicinski, etički i javnozdravstveni značaj neonatalnog skrininga. Srbija je 2021. pokrenula prvi genetički neonatalni skrining za SMA, centralizovan na Biološkom fakultetu Univerziteta u Beogradu, koji od 1997. ima ekspertizu u istraživanjima i dijagnostici SMA. U 17-mesečnoj studiji izvodljivosti testirano je 12,000 novorođenčadi iz dva porodilišta. Uzorci suvih krvavih mrlja analizirani su metodom qPCR radi otkrivanja odsustva gena SMN1, uz potvrdno testiranje i određivanje broja kopija SMN2 metodom MLPA. Nakon završetka studije izvodljivosti, nacionalni program skrininga za SMA počeo je 15. septembra 2023. i danas obuhvata 52 državna i 6 privatnih porodilišta. Do 9. septembra 2025. testirano je 119,735 novorođenčadi i identifikovano je 19 SMA pozitivnih beba. Od toga je 17 odmah započelo terapiju—6 sa dve kopije SMN2, 7 sa tri kopije i 4 sa četiri kopije—dok su dva novorođenčeta sa pet kopija pod kliničkim nadzorom. Lečene bebe su uglavnom ostali asimptomatski. Multidisciplinarna Stručna komisija za SMA donosi individualizovane odluke o terapiji, kombinujući genetičke, kliničke i laboratorijske podatke. Program je dao prvu pouzdanu procenu učestalosti SMA u Srbiji (1:6,302) i pokazao da presimptomatska dijagnoza, jasno definisani protokoli i personalizovana terapija mogu SMA pretvoriti iz teškog, životno ograničavajućeg oboljenja u (iz)lečivu bolest. Srpsko iskustvo pruža model za integraciju precizne medicine u nacionalne zdravstvene sisteme kroz saradnju akademske zajednice, pacijenata, industrije i države