A novel IDS variant associated with an isolated ocular phenotype in Hunter syndrome

Introduction: Hunter syndrome (mucopolysaccharidosis type II, MPS II) is an X-linked lysosomal storage disorder caused by iduronate-2-sulfatase (IDS) mutations and is classically associated with multiple-organ-systems involvement. Ocular findings are usually reported in conjunction with systemic manifestations, and isolated ocular presentations have not been well characterized. Here, we report a novel hemizygous IDS variant in a patient who initially presented with isolated corneal and retinal pathology and was subsequently diagnosed with attenuated Hunter syndrome. Methods Case report of a patient presenting with isolated corneal and retinal degeneration, evaluated using multimodal retinal imaging and full-field electroretinography. Results A 44-year-old male with progressive nyctalopia demonstrated bilateral parafoveal and peripheral retinal depigmentation with central macular sparing on optical coherence tomography and a symmetric bull’s-eye pattern on fundus autofluorescence. Visual field testing revealed bilateral ring scotomas, and full-field electroretinography showed subnormal rod-predominant responses. Pedigree analysis suggested X-linked inheritance. Genetic testing identified a novel hemizygous IDS variant (c.707A > G, p.Lys236Arg), and the diagnosis of Hunter syndrome was supported by markedly reduced IDS activity and elevated urinary glycosaminoglycans with increased heparan sulfate. Conclusion A novel missense IDS mutation was identified in association with Hunter syndrome, highlighting the importance for ophthalmologists to consider MPS II in patients presenting with isolated retinopathy and the value of genetic diagnosis in revealing atypical systemic disease.