ROSAH syndrome mimicking chronic uveitis

Area of Science:

• Genetics
• Ophthalmology
• Rare Diseases

Background:

• ROSAH syndrome is a rare autosomal dominant multi-systemic disorder.
• Key features include retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headaches.
• Previous genetic causes remained elusive.

Purpose of the Study:

• To identify the genetic basis of ROSAH syndrome.
• To characterize the ophthalmological and systemic manifestations.
• To propose a candidate variant for targeted therapy.

Main Methods:

• Longitudinal follow-up of five patients from two unrelated families.
• Clinical examination for ophthalmological and systemic signs.
• Genetic analysis including Next Generation Sequencing (NGS) and Whole-Genome Sequencing (WGS).

Main Results:

• Ophthalmological findings included extensive optic nerve swelling, macular edema, and vascular leakage.
• Systemic manifestations comprised recurrent fever, splenomegaly, anhidrosis, mild cytopenia, anicocytosis, and hypersegmented neutrophils.
• All patients shared a heterozygous missense variant in ALPK1: c.710C>T; p.(Thr237Met).

Conclusions:

• A unique missense variant in ALPK1 is strongly associated with ROSAH syndrome.
• Ophthalmological features are the primary morbidity.
• Early genetic diagnosis and potential gene correction therapy are feasible.