目的 总结低磷酸酯酶血症（hypophosphatasia, HPP）患儿的临床、遗传学特征及随访情况。 方法 回顾性分析2018年1月—2025年8月就诊于上海儿童医学中心的12例HPP患儿的临床资料、基因检测结果及随访结果。 结果 12例HPP患儿中，婴儿型1例、儿童型8例、牙型3例，常见表现为乳牙非创伤性早失（11例）、骨骼畸形（6例）和身材矮小（5例）；首发症状中位年龄为23.50月龄，临床诊断中位年龄为38.50月龄。儿童型HPP患儿的血清碱性磷酸酶标准差评分低于牙型患儿（P<0.05）。共检出19个ALPL基因变异，其中6种既往未见报道，分别为c.191T>A（p.Val64Asp）、c.1407C>A（p.His469Gln）、c.351C>G（p.Tyr117Ter）、c.1007T>C（p.Ile336Thr）、c.1280delins14（p.Glu427Glyfs*）和c.181+5G>C；7例检出复合杂合变异，5例检出杂合变异；3例牙型患儿仅检出单个杂合变异。 结论 HPP患儿临床和遗传学特征具有异质性，临床诊断存在一定延迟。乳牙非创伤性早失、ALPL基因变异是HPP的重要特征，不同亚型血清碱性磷酸酶水平有显著差异，对疑似患儿应尽早完善碱性磷酸酶检测和ALPL基因分析。
Objective To summarize the clinical and genetic characteristics and follow-up data of children with hypophosphatasia (HPP). Methods A retrospective analysis was conducted of 12 children with HPP who were treated at Shanghai Children's Medical Center between January 2018 and August 2025, including clinical features, genetic testing results, and follow-up data. Results Of the 12 children, 1 had infantile HPP, 8 had childhood HPP, and 3 had odonto-HPP. Common manifestations included non-traumatic premature loss of primary teeth (n=11), skeletal deformities (n=6), and short stature (n=5). The median age at symptom onset was 23.50 months, and the median age at clinical diagnosis was 38.50 months. The serum alkaline phosphatase standard deviation score was lower in children with childhood HPP than in those with odonto-HPP (P<0.05). A total of 19 ALPL variants were identified, six of which had not been previously reported: c.191T>A (p.Val64Asp), c.1407C>A (p.His469Gln), c.351C>G (p.Tyr117Ter), c.1007T>C (p.Ile336Thr), c.1280delins14 (p.Glu427Glyfs*), and c.181+5G>C. Seven children carried compound heterozygous variants, and five carried a single heterozygous variant. All three children with odonto-HPP carried only a single heterozygous variant. Conclusions HPP in children shows clinical and genetic heterogeneity, and clinical diagnosis may be delayed. Non-traumatic premature loss of primary teeth and ALPL variants are important features of HPP. There are significant differences in the levels of serum alkaline phosphatase among different subtypes. For suspected cases, serum ALP testing and ALPL genetic testing should be completed promptly.
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