Elevated iron levels in tears of patients diagnosed with WDR45 X-linked optic atrophy

Background: Pathogenic variants in WDR45 are associated with iron deposits in the basal ganglia. We aimed to determine iron levels in tears of patients with WDR45 X-linked optic atrophy compared to healthy controls. Methods: The study group included two brothers aged 26 and 32 years and a 3-year-old girl from another family diagnosed with optic atrophy, all of whom harbored a novel pathogenic variant in WDR45. Tear samples were collected from the inferior fornix using Schirmer filter strips and analyzed for trace elements using a particle-induced X-ray emission (PIXE) technique and a Fast X123 SDD70 (C2) detector. Concentrations were calculated as the difference from unused Schirmer strips. Findings were compared with 28 healthy subjects, 21 females and 7 males, aged 18–50 years (mean 28.5 ± 9.09 years). Results: All three patients with WDR45 X-linked optic atrophy exhibited elevated iron levels in their tears compared to healthy controls. No differences from the control group were detected for other trace elements. Conclusions: This is the first study to show higher-than-normal iron levels in the tears of patients with X-linked optic atrophy due to a variant in WDR45. The findings broaden our understanding of the role of the WDR45 gene in disorders related to abnormal iron pathophysiology. PIXE analysis is a highly sensitive technique for measuring trace elements in tears. Further clinical studies are needed to investigate potentially novel genotype-phenotype correlations. The application of these findings in clinical practice may benefit patient care.