Spectrum of inherited metabolic disorders diagnosed through newborn screening and symptomatic referrals in Eastern Türkiye.

OBJECTIVE: Inherited metabolic disorders (IMDs) are heterogeneous genetic diseases whose observed spectrum is influenced by population characteristics, newborn screening (NBS), and diagnostic pathways.This study aimed to characterize confirmed IMDs diagnosed through NBS and symptomatic referrals at a tertiary center in Eastern Türkiye and estimate the regional burden of selected disorders. METHODS: This retrospective study included patients evaluated between September 2022 and September 2024. IMDs were confirmed by biochemical and/or molecular genetic analyses. Population and live-birth data from the defined referral region were used to estimate regional and NBS-based birth prevalence. RESULTS: Among 9603 patients evaluated, 828 (8.6%) had a confirmed IMDs; 580 (70.0%) were identified through NBS, 230 (27.8%) through symptomatic referral, and 18 (2.2%) through family screening. Vitamin and cofactor metabolism (43.8%) and amino acid metabolism disorders (35.7%) predominated. Biotinidase deficiency was the most frequent disorder (n = 360, 43.4%), including 316 (87.8%) partial and 44 (12.2%) profound cases. Neurological manifestations were the most frequent presentation among symptomatic patients (23.2%). Based on 61,409 estimated live births, estimated birth prevalence was 1:627 for the hyperphenylalaninemia/phenylketonuria spectrum and 1:543 for biotinidase deficiency. Minimum estimated regional prevalence was 1.07 and 0.97 per 100,000 for mucopolysaccharidoses and alkaptonuria, respectively. CONCLUSION: NBS and symptom-based evaluation are complementary diagnostic pathways for IMDs. The observed disease spectrum reflects the influence of screening strategies, while symptomatic referrals reveal broader clinical and genetic heterogeneity.