IMPE Abstracts

Skeletal dysplasia (SD) and metabolic bone diseases (MBD) are congenital diseases which result in abnormalities in bone morphometry and mineral metabolism. Advances in molecular genetics research have revealed many gene variants that cause SD and MBD. In 2019, nosology and classification of genetic skeletal disorders was revised in which 437 different genes have been found in 425 (92%) of these disorders ¹⁾, and new genetic etiologies are continually being discovered. At present, molecular biological mechanisms of the pathogenesis have been elucidated based on functional analysis of identified pathogenic genes, and development of molecular-targeted drugs specific to the pathogenesis is progressing. For example, the pathophysiology of X-linked hypophosphatemic rickets is the loss of PHEX gene function caused by a variant, resulting in overproduction of fibroblast growth factor 23 (FGF23), which results in hypophosphatemia and rickets. Today, neutralizing antibody to FGF23 that specifically attenuate the action of overproduced FGF23 have been developed and clinically applied. In other skeletal dysplasia, achondroplasia which is caused by constitutively active mutation in FGFR3 gene, recombinant human C-type naturiuretic peptide, vosoritide has been developed as a novel therapy. Given such situations, it is more important than ever to accurately diagnose patients and provide appropriate therapeutic intervention. However, because SD and MBD are rare, even pediatric endocrinologists have limited opportunities for medical treatment to these patients. In addition, it is difficult to systematically experience these cases and make accurate diagnoses due to the wide variety of phenotype. In Meet The Expert 9.2, therefore, I will provide an overview of SD and MBD based on case presentations and discuss novel therapeutic developments. 1. Mortier GR, et al. Am J Med Genet A. 2019 Dec;179(12):2393-2419.