Clinical and Genetic Characteristics of Hypophosphatasia in Chinese Children

Abstract

Background: Hypophosphatasia (HPP) is a rare inherited disorder, which is caused by loss-of-function mutations in the ALPL gene. HPP is a heterogeneous disease that has a wide spectrum of phenotypes. Few studies were carried out in the Chinese population with HPP, especially in children. Methods: The clinical and genetic characteristics of 10 Chinese children with HPP who were referred to the Beijing Children’s Hospital were described. We also reviewed previously reported HPP cases of children in China.Results: A total of 33 cases were identified, which included 2 perinatal lethal, 10 infantile, 10 childhood, and 11 odonto types of HPP. The male to female ratio was 24:9. The average age at onset was 0.69 years (ranged from 2 hours after birth to 14 years), while the average age at clinical diagnosis was 3.87 years (ranged from 2 hours after birth to 19 years). Serum alkaline phosphatase (ALP) levels were significantly decreased in patients with severe forms of HPP (perinatal lethal/infantile HPP) when compared with those with the mild forms of HPP (childhood/odonto HPP, P<0.01). Although serum phosphate levels were not significantly different (P>0.05), serum calcium levels were elevated, and serum intact parathyroid hormone (i-PTH) levels were decreased in patients with severe forms of HPP in comparison with those with the mild forms of HPP (P all <0.01). Genetic analyses identified 40 mutations in 31 HPP cases, including 28 missense mutations, 9 frameshift mutations, 2 splice junction alterations, and 1 regulatory mutation. Of which, 5 novel mutations were identified in our present study: 2 frameshift mutation (p.Arg138GlyfsTer27, p.Leu511Profs*272); 2 missense mutations (p.Ala176Val, p.Phe268Leu), and 1 splice junction alterations (c.297+5G>A). Compound heterozygous mutations accounted for 89.29% of all variants. No mutational “hot-spot” was found. Most mutations of ALPL were located in exons 5, 7, 10 and 3. Notably, subjects that carrying single heterozygous mutations showed milder phenotypes of HPP, while subjects with nonsense mutations were associated with a severe phenotype.Conclusions: HPP is a rare disease with often delayed diagnosis, and the incidence of HPP in China may be seriously underestimated. The present study expands the phenotypic and genotypic spectrum and our understanding of HPP in Chinese children.These findings will be useful for clinical assessment and shorten the diagnostics of pediatric HPP in China.

Relação entre determinantes do estilo de vida e hábito de exposição solar no estado nutricional de crianças portuguesas

“…Compared with preschoolers, school-aged children had longer exposure to the sun (210.6 ±44.4 minutes vs. 208.2 ±45 minutes/day) with age being a factor that influences vitamin D status (Rutigliano et al, 2021). On the other hand, in the study Studies show that children with overweight or obesity tend to be less physically active and that physical activity reduces the risk of obesity (Raistenskis et al, 2016;Hong et al, 2016;Liu et al, 2021). Therefore, the practice of physical activity is included in most interventions for the prevention and treatment of childhood obesity (Janssen, 2014).…”