Orodental phenotype and genotype findings in 8 Chinese children with hypophosphatasia

Abstract

Objective: To analyze the oral phenotype and gene variation of children with hypophosphatasia (HPP), and explore the genotype-phenotype correlations. Methods: Eight children diagnosed with HPP from January 2008 to January 2023 in Children's Hospital,Zhejiang University School of Medicine were recruited in this study. The pathogenic genes of 5 of them were sequentially analyzed and all of their oral manifestations, laboratory tests and genetic variation types were retrospectively analyzed. Results: A total of 8 children were recruited in the study, 3 males and 5 females, aged from 20 months to 104 months, whose main complaints were premature deciduous tooth loss. Among them, 3 children were diagnosed with odonto HPP, and the other 5 children were diagnosed with childhood HPP, including 2 children was odonto HPP at the first diagnosis and modified as childhood HPP at the age of 5. The age range of first deciduous tooth loss is 9 to 18 months, and the age range of diagnosis is 20 to 104 months. The patients of odonto HPP only showed premature loss of deciduous anterior tooth, while the patients with childhood HPP also showed premature loss of multiple deciduous molars. Panoramic radiographic film revealed enlarged pulp chambers and radicular canals in some primary and permanent teeth. The enamel hypoplasia, hypoplastic short roots, and alveolar resorption of deciduous molar were observed in some cases. The serum alkaline phosphatase (ALP) (30-107 U/L) levels of all the patients were lower than that in the normal children of same age and gender, and the ALP value of the 1-3 years old girls with childhood HPP (30-33 U/L) was lower than that of the three children with odonto HPP (61-107 U/L), but there was no significant difference in statistical analysis. There were 8 variation sites of ALP liver/bone/kidney (ALPL) gene detected in 5 children and their families, all of which were missense variation, including the new variants in the mutations of c.1334C>G(p.Ser445Cys) and c.1259G>T(p.Gly420Val) that were not reported in the literature. One case was autosomal dominant inheritance and other 4 cases were complex heterozygous variation with autosomal recessive inheritance. Conclusions: Pediatric stomatologists are often the first doctors to detect childhood and odonto HPP. Diagnosis of mild HPP is often delayed. The severity of HPP is related to serum ALP level and ALPL gene mutation sites.