Juvenile Paget disease

Juvenile Paget disease (JPD), also known as hereditary hyperphosphatasia, hyperostosis corticalis deformans juvenilis, or chronic congenital idiopathic hyperphosphatasia, is an extremely rare inherited metabolic bone disorder characterized by markedly accelerated bone turnover throughout the skeleton. Unlike classic Paget disease of bone, which typically affects older adults and involves focal skeletal lesions, JPD presents in early childhood with generalized skeletal involvement. The condition is caused by mutations in the TNFRSF11B gene (also known as OPG, encoding osteoprotegerin), which plays a critical role in regulating osteoclast activity and bone resorption. The disease primarily affects the skeletal system, leading to progressive skeletal deformities, bone pain, fractures, short stature, and widening of the long bones and skull. Affected children typically present in infancy or early childhood with an expanding skull, bowing of the limbs, kyphoscoliosis, and difficulty walking. Hearing loss may develop due to involvement of the temporal bones. Laboratory findings characteristically show markedly elevated serum alkaline phosphatase levels and increased urinary hydroxyproline, reflecting the dramatically accelerated bone remodeling. Radiographically, bones appear expanded with thickened but structurally abnormal cortices and a cotton-wool appearance of the skull. Treatment focuses on reducing the excessive bone turnover and managing symptoms. Bisphosphonates, particularly intravenous pamidronate, have been used with some success in reducing bone pain, normalizing biochemical markers, and improving bone density and structure. Calcitonin has also been used historically but is generally less effective than bisphosphonates. Orthopedic interventions may be necessary for fracture management and correction of skeletal deformities. Early diagnosis and treatment are important to minimize skeletal complications and improve quality of life.

Common questions about Juvenile Paget disease