Potential therapeutic response in a severe case of autosomal dominant osteopetrosis type I

The low-density lipoprotein receptor-related protein 5 gene (LRP5), which encodes a coreceptor within the canonical Wnt signaling pathway, plays a crucial role in bone mass regulation and has been associated with several bone disorders. Autosomal dominant osteopetrosis type I (ADO type I, OMIM 607634) is a rare disease caused by heterozygous, gain-of-function mutations in LRP5. Here we describe a 44-year-old female who presented with thickened calvarium, elevated bone density, torus palatinus, mandibular exostoses, enlarged mandible, and disabling headaches and bone pain. Exome sequencing revealed a previously reported heterozygous missense variant in the LRP5 gene (p.A242T). Post-diagnosis cranial vault volume measurement by computed tomography 3D reconstruction demonstrated decreasing intracranial volume over time. Off-label use of leuprolide acetate was associated with apparent stabilization of skull mineralization. This report documents a severe example of ADO type I and provides anecdotal evidence of the utility of therapy in need of formal evaluation.