Clinical and genetic characteristics of hypophosphatasia in Chinese children

作者：Meijuan Liu, Min Liu, Xuejun Liang, Di Wu, Wenjing Li, Chang Su, Bingyan Cao, Jiajia Chen, Chunxiu Gong · 发表于：Orphanet Journal of Rare Diseases · 年份：2021 · DOI：10.1186/s13023-021-01798-1 · 被引用次数：19 · 研究领域：Alkaline Phosphatase Research Studies、Bone health and treatments、Bone health and osteoporosis research

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. Previously reported HPP cases of children in China were also reviewed. RESULTS: A total of 33 cases were identified, which included 2 perinatal lethal HPP, 10 infantile HPP, 10 childhood HPP, and 11 odonto HPP. The male-to-female ratio was 24:9. The average age at onset was 0.69 years (ranged from 2 h after birth to 14 years), while the average age at clinical diagnosis was 3.87 years (ranged from 2 h after birth to 19 years). Serum alkaline phosphatase (ALP) levels were significantly decreased in patients with 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 different (P > 0.05), serum calcium levels were elevated, and serum intact parathyroid hormone levels were decreased in patients with perinatal lethal/infantile HPP in comparison with those with the childhood/odonto 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 ...