Juvenile Paget's Disease: Report of a successful treatment throughout the complete growth of a patient with a missense TNFRSF11B mutation

Abstract

Introduction: Juvenile Paget's Disease (JPD) is an ultra-rare inherited osteopathy featuring markedly accelerated bone turnover. Several clinical characteristics have been reported, including bone deformities developing in childhood and hearing loss.

Case report: We report the case of a 2 ¾-year-old girl that presented with progressive bowing of both legs since the age of 2, lower limb pain and frequent falls with one consequent femur fracture. Plain radiographs revealed osteoectasia of the long bone's diaphysis, and laboratory tests showed extremely high serum total alkaline phosphatase levels. A missense mutation on the gene TNFRSF11B was identified in homozygosity, and the diagnosis of JPD was made. Treatment with bisphosphonates was initiated early and markedly improved lower limb bowing and pain. The patient reached adulthood with normal height, minor bone deformities, and no functional impairment. Despite the good skeletal symptom's response, bisphosphonates failed to prevent or improve sensorineural hearing loss.

Conclusions: In this clinical case, early treatment with bisphosphonates was effective for the treatment of JPD skeletal deformities. New therapeutic strategies need to be developed to better control the extraskeletal manifestations of JPD.

Keywords: Bisphosphonates; Case report; Juvenile Paget's Disease.