Mineralization Defects in the Primary Dentition Associated With X-Linked Hypophosphatemic Rickets

X-linked hypophosphatemia rickets (XLH) is caused by inactivating mutations in the phosphate-regulating endopeptidase homolog, X-linked (PHEX) gene, leading to renal phosphate wasting and hypophosphatemia. Dental mineralized tissues are affected by XLH, though tissue-specific dental mineralization defects have been variably described. We aimed to quantify dental effects in primary teeth of six pediatric patients with XLH (four females and two males, aged 5-12 years). All participants had received conventional treatment of calcitriol and phosphate from initial diagnosis. High-resolution mu CT and histology were employed to analyze 15 exfoliated or extracted primary teeth from patients in comparison with primary control teeth from healthy children. Compared with controls, a third of the teeth from patients with XLH showed reduced enamel density, though enamel thickness was not reduced. Teeth from patients with XLH featured 10% reduction in mean dentin density, though teeth from three affected individuals had dentin densities within normal limits. Dentin mineralization defects were found across all regions of dentin in affected teeth: outer mantle dentin, circumpulpal dentin, and the most recently formed proximal pulpal dentin. Both crown and root dentin thickness appeared reduced in XLH-affected versus control teeth, with root dentin more severely affected. Interglobular dentin accumulation throughout the circumpulpal dentin was evident by both mu CT and histology (585-fold volume increase and 45-fold area increase, respectively). Histology also revealed substantially wider predentin and decreased acellular cementum thickness in XLH-affected versus control teeth, though thinner cementum appeared to include functionally oriented Sharpey's fibers except in the most severely affected individuals. These data provide quantitative analyses of dental mineralization defects associated with XLH, finding a wide range of severity, with dentin more significantly and consistently defective across the spectrum of XLH.

Automated summary

This study quantified dental effects in primary teeth of pediatric XLH patients, finding reduced enamel density in a third of the teeth and a 10% reduction in mean dentin density. Dentin mineralization defects were present in all regions of dentin in affected teeth, with both crown and root dentin thickness reduced in XLH-affected teeth.