Hyperostosis–Hyperphosphatemia Syndrome: A Congenital Disorder of <i>O</i>-Glycosylation Associated With Augmented Processing of Fibroblast Growth Factor 23

Abstract

The primary defect in HHS is impairment of glycosylation of FGF23 resulting from mutations in GALNT3 and leading to augmented processing of FGF23. These changes in FGF23 abolish its phosphaturic effect and lead to severe persistent hyperphosphatemia. This study provides the pathogenetic mechanism of the first mucin-type O-glycosylation defect identified.