Assessment of Vitamin D Status and Calcium-Phosphate Metabolism in Patients with Hypophosphatasia-A Single-Center Cohort Study.

Background

Hypophosphatasia (HPP) is a rare genetic disorder caused by a loss-of-function mutation in the ALPL gene, which encodes tissue-nonspecific alkaline phosphatase (TNSALP). Reduced TNSALP activity in HPP primarily leads to bone mineralization disorders. Given the complex and challenging nature of issues related to vitamin D and HPP, it is essential to evaluate each patient individually and adjust the appropriate dose of vitamin D according to their specific needs in order to maintain calcium phosphate homeostasis and normal vitamin D levels. Maintaining proper vitamin D homeostasis in patients with hypophosphatasia is one of the greatest challenges.

Objective

The objective of this study was to conduct a retrospective, comprehensive assessment of calcium-phosphate metabolism, with particular emphasis on vitamin D status in patients with genetically confirmed hypophosphatasia (HPP), and to identify potential correlations between 25(OH)D concentrations and other parameters of calcium-phosphate in this group of patients.

Methods

A single-center, retrospective pilot study was conducted in a small cohort (n = 36) of patients suffering from an ultra-rare genetic disorder, hypophosphatasia. The small sample size reflects the ultra-rare nature of the disease; so far, HPP has been diagnosed in approximately 50 patients in Poland (prevalence 1:300,000). The analysis included medical records of patients.

Results

Vitamin D deficiency was not observed in the majority of patients with hypophosphatasia in the study group. The initiation of long-term enzyme replacement therapy (with asfotase alfa) did not significantly affect the annual change in mean serum vitamin D concentration. As established in the literature, growth disorders are an inherent feature of the clinical picture of hypophosphatasia. This was reflected in our study group, where nearly half of the pediatric patients achieved a height below the 10th percentile.

Conclusions

Within this limited sample, these growth issues did not appear to be associated with disturbances in calcium and phosphate metabolism or vitamin D deficiency.