Early-onset juvenile Paget disease associated with a homozygous intronic TNFRSF11B variant: a 2-year follow-up

Abstract

Abstract Objectives Juvenile Paget disease (JPD) is an ultra-rare inherited metabolic bone disorder characterized by excessive skeletal turnover secondary to osteoprotegerin (OPG) dysfunction. Early diagnosis is important because progressive skeletal and extraskeletal complications may develop during infancy and childhood. Case presentation We report a 2-month-old infant presenting with severe irritability and pain even with gentle movement, femoral swelling, and persistent hyperphosphatasemia. Skeletal survey demonstrated findings compatible with JPD. Genetic analysis identified a rare homozygous intronic TNFRSF11B variant. Pamidronate treatment resulted in marked biochemical and clinical improvement, including a marked reduction in alkaline phosphatase levels compared with baseline values, resolution of pain, and preservation of neuromotor developmental milestones during the 2-year follow-up period. Cardiovascular evaluation, vascular imaging, and ophthalmologic examinations revealed no abnormalities. Conclusions This case highlights the diagnostic challenges of early-onset JPD and supports the importance of careful clinical, radiologic, and genetic evaluation in infants with persistent hyperphosphatasemia and skeletal abnormalities. Although early bisphosphonate therapy effectively improved skeletal disease activity, extraskeletal manifestations may still occur during follow-up, highlighting the need for continued long-term surveillance.