Pycnodysostosis (PYCD) is a rare recessive inherited skeletal disease, characterized by short stature, brittle bones, and recurrent fractures, caused by variants in the Cathepsin K encoding gene that leads to impaired osteoclast-mediated bone resorption. Hypophosphatasia (HPP) is a dominant or recessive inherited condition representing a heterogeneous phenotype with dental symptoms, recurrent fractures, and musculoskeletal problems. The disease results from mutation(s) in the tissue non-specific alkaline phosphate encoding gene with reduced activity of alkaline phosphatase and secondarily defective mineralization of bone and teeth. Here, we present the first report of a patient with the coexistence of PYCD and HPP. This patient presented typical clinical findings of PYCD, including short stature, maxillary hypoplasia, and sleep apnoea. However, the burden of disease was caused by over 30 fractures, whereupon most showed delayed healing and non-union. Biochemical analysis revealed suppressed bone resorption and low bone formation capacity. We suggest that the coexistence of impaired bone resorption and mineralization may explain the severe bone phenotype with poor fracture healing.
Bibliografisk noteFunding Information:
NH, PV, HBH, KH, ALF, MD, and NRJ have nothing to disclose. Jens-Erik Beck Jensen (JEBJ) was a board member in Eli Lilly, Amgen and MSD. JEBJ received funding from Eli Lilly and Amgen and consulting fees from MSD, Giliad and Amgen. Bente Langdahl (LB) received research grants from Novo Nordisk and Amgen. LB has received personal fess by acting on advisory boards and giving lectures from Amgen, UCB, Eli Lilly and TEVA.
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