ROSAH syndrome

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Synonyms

Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis and Headache,

Overview

ROSAH syndrome is an autoinflammatory disease with a highly variable phenotype, including (in addition to the ROSAH-defining features) recurrent fever, cytopenias, dental and nail abnormalities, sicca syndrome, and meningeal inflammation on brain MRI.

Symptoms

Retinal Dystrophy: This involves progressive vision loss and degeneration of the retina, potentially leading to counting fingers or no light perception by the third decade of life. 

Optic Nerve Edema: Swelling of the optic disc, which can be seen during an eye exam. 

Splenomegaly: Enlargement of the spleen, which can be detected by palpation or imaging. 

Headaches: Migraine-like headaches are common. 

Ocular Inflammation: Including uveitis, cystoid macular edema, and retinal detachment. 

 

Causes

ROSAH syndrome is caused by a gain-of-function mutation in the ALPK1 gene, which encodes a protein that acts as a sensor for bacterial sugars in the innate immune system. This mutation leads to overactivation of the NF-κB pathway, a key regulator of inflammation

Diagnosis

ROSAH syndrome, also known as ALPK1-related autoinflammatory disease, is diagnosed through a combination of clinical findings and genetic testing. The diagnosis is suggested by the characteristic symptoms of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache, along with other systemic features. Genetic testing, specifically sequencing of the ALPK1 gene, confirms the diagnosis by identifying disease-causing mutations. 

Clinical Features
Ocular:

Optic nerve edema (swelling of the optic disc) 

Uveitis (inflammation of the middle layer of the eye) 

Retinal dystrophy (degeneration of the retina) 

Retinal vasculitis (inflammation of retinal blood vessels) 

Macular edema (swelling of the macula, the central part of the retina) 
Systemic:

Splenomegaly (enlarged spleen)

Recurrent fevers 

Anhidrosis (inability to sweat) 
Headaches (including migraine-like symptoms) 
Arthritis (joint pain and inflammation) 
Cytopenias (low blood cell counts) 
Dental abnormalities 

Skin problems 

Diagnostic Tests

Ophthalmological Examination:

Dilated fundus examination: To assess the retina, optic nerve, and blood vessels. 

Optical coherence tomography (OCT): To evaluate retinal thickness and detect macular edema. 
Fluorescein angiography: To assess retinal blood vessel leakage and inflammation. 
Electroretinography (ERG): To evaluate the function of the retina’s light-sensitive cells. 
Visual field testing: To identify blind spots in the visual field. 
Fundus autofluorescence (FAF): To assess the health of the retinal pigment epithelium. 

Genetic Testing:

Sequencing of the ALPK1 gene is crucial for confirming the diagnosis

Prognosis

ROSAH syndrome, characterized by Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis, and Headache, has a variable prognosis. While the exact prognosis is still being researched, it’s known that the visual impairment can progress to severe loss, potentially leading to blindness, by the third decade of life. However, some patients show improvement with treatments like interleukin-6 (IL-6) inhibitors. Other systemic symptoms like fever and cytopenias can also be managed with biologics.

Treatment

There is no cure for ROSAH syndrome, but treatments are available to manage the symptoms and reduce inflammation. Biologic drugs that target specific inflammatory pathways (such as TNF, IL-1, and IL-6) have shown promise in some cases. Early diagnosis and treatment are important to help preserve vision and manage other symptoms.