Carrier Frequency of Neurodegeneration with Brain Iron Accumulation ( <scp>NBIA)</scp> Disorders in a Middle Eastern Clinical Cohort Based on Retrospective Genetic Testing Data

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) is a group of inherited disorders characterized by iron accumulation in the basal ganglia. Although the prevalence is estimated at 0.1-0.3 per 100,000,000 individuals, epidemiological data remain limited. OBJECTIVES: To determine the carrier frequency and lifetime risk ratios of autosomal recessive NBIA disorders within a Middle Eastern cohort by screening eight established NBIA genes in a large regional exome cohort. METHODS: Variants in NBIA-associated genes were analyzed in 16,769 individuals using whole-exome sequencing, clinical-exome sequencing, and TruSight One panels. RESULTS: The lifetime risk of autosomal recessive NBIA disorders was estimated at 3.43 per 1,000,000 individuals (95% CI 1.43-6.46). PLA2G6 contributed the largest proportion of the estimated disease burden, followed by PANK2 and C19orf12. CONCLUSIONS: This is the first systematic analysis of lifetime risk and carrier frequencies of NBIA in Middle Eastern populations. The findings suggest a notable carrier frequency and highlight the need for region-specific genetic screening. © 2026 International Parkinson and Movement Disorder Society.