pycnodysostosis
Pycnodysostosis is a rare skeletal dysplasia with bone abnormalities such as short stature, acroosteolysis of distal phalanges, and skull deformities.
Etiology
mutations in the cathepsin K gene disrupting wild type cathepsin K activity have been described in patients with pycnodysostosis.
deficiency of the cysteine protease cathepsin K, responsible for degradation of collagen type I and other bone proteins.
Osteoclasts, bone cells of hematopoietic origin responsible for bone mineral as well as protein matrix degradation, are dysfunctional in patients with pycnodysostosis due to mutations in the cathepsin K gene. Cathepsin K deficient osteoclasts can demineralize bone but cannot degrade the protein matrix.
References
Motyckova G, Fisher DE. Pycnodysostosis: role and regulation of cathepsin K in osteoclast function and human disease. Curr Mol Med. 2002 Aug;2(5):407-21. PMID: #12125807#