Renal Disease in ROSAH Syndrome Masquerading as Lupus Nephritis: A Case Report and Cohort Analysis

ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare, autosomal dominant autoinflammatory disorder caused by gain-of-function mutations in ALPK1. These mutations activate NF-κB signaling and drive development of a multisystemic disease. Beyond the hallmark features captured in the ROSAH acronym, affected individuals may experience recurrent low-grade fevers, deforming arthritis, and gastrointestinal inflammation. Prior to the identification of a unifying genetic cause, patients can be misdiagnosed with a range of immune-mediated conditions, such as systemic juvenile idiopathic arthritis, multiple sclerosis, and systemic lupus erythematosus. Here, we report a 44-year-old man who was given a diagnosis of lupus nephritis before being found to have ROSAH. He presented with mild chronic kidney disease and subnephrotic proteinuria. Renal biopsy revealed immune complex-mediated glomerulonephritis with minimal mesangial proliferation, resembling class II lupus nephritis, despite the absence of clinical or serological markers of systemic lupus erythematosus. In parallel, we leveraged the world's largest reported single-center ROSAH cohort to assess the prevalence of chronic kidney disease in this rare genetic syndrome.