ROSAH (Retinal dystrophy, Optic nerve edema, Splenomegaly, Anhidrosis, Headache) syndrome is caused by a gain-of-function mutation in the ALPK1 gene and is classified as a systemic autoinflammatory disease due to constitutive activation of the NF-κB pathway. Ocular symptoms are the most frequent initial presentation; however, splenomegaly in early childhood rarely leads to a diagnosis.
A 4-year-old boy was diagnosed with splenomegaly at a local hospital and referred to our department at the age of 5 years. At 9 years of age, he developed recurrent fever; at 10 years of age, thrombocytopenia and bilateral abducens nerve palsy appeared; and at 12 years of age, papilledema and retinal degeneration were observed. At 14 years of age, he developed macular edema and uveitis. Prednisolone was administered; however, it was ineffective. Whole-exome analysis performed at 15 years of age in 2017 failed to identify a disease-associated gene, as the causative gene for ROSAH syndrome was discovered in 2019. At 20 years of age, comprehensive genetic analysis identified a heterozygous ALPK1 c.710C>T (p.Thr237Met) variant, confirming the diagnosis of ROSAH syndrome. At 23 years of age, anemia and positive fecal occult blood were observed, and both upper and lower gastrointestinal endoscopies were performed; however, no signs of inflammatory bowel disease were found. Currently, he continues to experience periodic fever of 38–39°C with associated elevation of C-reactive protein (CRP), recurring almost every 7 days, and his visual impairment is progressing. In addition, during the course of his illness, he exhibited general fatigue, loss of appetite, decreased sweating, reduced saliva secretion, dental caries, odontoma, hyperuricemia, thoracic vertebral malformation, and conjunctival dermoid. He did not experience headache or joint pain.
ROSAH syndrome should be considered in the differential diagnosis of unexplained splenomegaly and thrombocytopenia in early childhood. Multifaceted evaluations, including ophthalmological findings, inflammatory markers, abnormal sweating, dental caries, and genetic testing, are useful for early diagnosis. Although some studies have reported the effectiveness of treatments such as tocilizumab, they are generally insufficient to prevent the progression of visual impairment, highlighting the need for the development of new treatment options.
