Natural history of hypophosphatasia in Chinese patients younger than 18 years: a single-center retrospective observational study.

PURPOSE: To summarize the clinical features, natural history, and ALPL variant spectrum of Chinese children with hypophosphatasia (HPP), and to evaluate diagnostic features across clinical subgroups.

METHODS

This single-center retrospective observational study included children diagnosed with hypophosphatasia at our hospital who had not received enzyme replacement therapy. Published Chinese pediatric hypophosphatasia cases were also reviewed and combined with the single-center cohort for descriptive analyses.

RESULTS

Ninety-two children were included in the pooled cohort, comprising 23 patients in the single-center cohort and 69 cases identified from the literature. Baseline features were broadly comparable between single-center cohort and the literature cohort (P > 0.05). In the pooled cohort, there were 34 severe HPP (including 6 perinatal hypophosphatasia and 28 infantile hypophosphatasia), 34 childhood HPP, and 24 odonto-HPP. Median ages at onset were 0.09, 1.13, and 1.45 years, and median diagnostic delays were 0.15, 3.00, and 1.44 years, respectively. Height and weight Z-scores were lowest in severe HPP and least affected in odonto-HPP (all P < 0.001). Severe HPP had lower alkaline phosphatase, phosphate, and parathyroid hormone levels and higher calcium levels than the other groups. Among 70 genetically tested patients, 85 ALPL variants were identified; compound heterozygosity (78.6%) and missense variants (72.9%) predominated. In our single-center cohort, 3/8 severe HPP patients died, 4/9 childhood HPP patients progressed, and all 6 odonto-HPP patients remained stable during follow-up.

CONCLUSION

Chinese pediatric hypophosphatasia is clinically and genetically heterogeneous. Earlier onset was associated with more severe biochemical abnormalities, impaired growth, and poorer outcomes. Childhood hypophosphatasia was prone to diagnostic delay and did not show spontaneous resolution. Atraumatic early loss of primary teeth and persistently low age- and sex-adjusted alkaline phosphatase are key to early recognition. However, larger prospective studies are required to confirm these observations.