Ocular manifestations of ROSAH syndrome caused by different mutations of the ALPK1 gene.

Abstract

PURPOSE This study aims to elucidate the ocular manifestations and disease progression of ROSAH syndrome, which is attributed to different mutations of the ALPK1 gene. DESIGN Observational case series. METHODS A cohort of five patients from four distinct families diagnosed with ROSAH syndrome was recruited for this investigation. Comprehensive ophthalmic assessments were conducted, including best corrected visual acuity (BCVA), fundus photography (FP), B-ultrasound imaging, electroretinography (ERG), optical coherence tomography (OCT), visual field (VF) testing, and fundus autofluorescence (FAF). Additionally, systemic evaluations including abdominal ultrasonography and blood tests were performed. Whole exome sequencing (WES) was utilized to identify pathogenic variants, and in silico algorithms were employed to assess their pathogenicity. The patients were followed up for one to five years to evaluate the progression of the disease. RESULTS The age of the patients varied from 5 to 33 years, with visual acuity ranging from hand motion to 0.6. All patients exhibited optic disc edema and significant, persistent vitreous inflammatory opacities as observed in B-scan imaging. Each patient presented with retinal dystrophy, characterized by varying degrees of patchy pigment alterations on FP, differing extents of hypo-fluorescence on FAF, concentric reductions in VF, and varying degrees of ellipsoid zone (EZ) signal loss on OCT. ERG results indicated substantial retinal dysfunction, with rod photoreceptor function typically more reduced than that of cone photoreceptors. Three patients were found to carry the recurrent T237M variant of the ALPK1 gene, while two patients from a single family exhibited a novel T237A variant. Notably, individuals with the T237A variant displayed solely ocular manifestations, with no/mild systemic symptoms. CONCLUSIONS ROSAH syndrome is characterized by ocular manifestations that include persistent optic disc edema and a gradually progressive retinal degeneration, resembling retinitis pigmentosa (RP). Ocular symptoms may serve as the initial presentation or the exclusive manifestation in patients with ROSAH syndrome. Furthermore, we have identified a novel mutation in the ALPK1 gene that correlates with a relatively mild phenotype of ROSAH syndrome.