Clinical and genetic characteristics and follow-up of 12 children with hypophosphatasia

To summarize the clinical and genetic characteristics and follow-up data of children with hypophosphatasia (HPP).

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.

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.

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.