ESPE Abstracts

Objective: Hypophosphatasia (HPP) is a monogenic metabolic bone disease characterized by skeletal and dental mineralization disorders and paradoxically low serum alkaline phosphatase (ALP) activity. The pathogenic gene for HPP is ALPL, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). The purpose of this study is to determine the prevalence of HPP among the population in Suzhou and explore the genotypic spectrum of ALPL gene in Suzhou.

Method: Adult individuals with ALP levels below 40 U/L were selected from a population receiving annual health check-ups. Whole blood samples were collected for genetic testing and 5'-pyridoxal phosphate (PLP) measurement. For any identified ALPL gene variants with unclear pathogenicity, in vitro functional tests were conducted to evaluate the enzyme activity. The prevalence of HPP in the population was calculated based on the number of positive genetic test results and the total screened population. High-frequency variants were analyzed based on the genetic test results. ROC curve analysis was used to assess the efficiency of ALP and PLP values for HPP screening.

Results: The total study population comprised 23,430 individuals, of whom 246 had ALP levels below 40 U/L. After excluding individuals with secondary causes of low ALP levels and those who declined to participate, 145 participants were included in the study. Comprehensive ALPL gene sequencing and PLP testing were performed on the participants, identifying 43 individuals carrying pathogenic ALPL variants. Based on statistical calculations, the estimated prevalence of HPP in the population was approximately 1/545 to 1/321. Twenty-three different ALPL gene mutations were identified during screening, with six mutations appearing repeatedly (≥3 times). The high-frequency variants accounted for 58.1% of the total detected mutations. The area under the ROC curve for PLP values was 0.838, with an optimal cutoff value of 16.63 ng/ml, yielding a sensitivity of 86.4% and a specificity of 72.1%. The area under the ROC curve for ALP values was 0.805, with an optimal cutoff value of 31.5 U/L, providing a sensitivity of 59.1% and a specificity of 91.9%.

Conclusion: The estimated overall prevalence of HPP in the population ranges from approximately 1/545 to 1/321. In the Suzhou region, high-frequency ALPL gene variants account for a significant proportion of all identified variants, making them suitable for subsequent carrier screening. ALP can serve as a primary screening indicator for HPP, while PLP can be used as a secondary screening indicator.