Phenotype and genotype of hypophosphatasia cases in Saudi Arabia: multi-center case cohort.

Introduction: Hypophosphatasia (HPP) is a rare inherited metabolic disease caused by mutations in the Methods: This retrospective multicenter case series included six centers in Saudi Arabia. Paediatrics and adult patients with clinically and genetically confirmed HPP were included between January 2014 and May 2024. Demographic and clinical information, including medical history, clinical, biochemical, genetic, and management data, was collected retrospectively from medical records and summarized descriptively. Additionally, whole-exome sequencing or ALPL next-generation sequencing (NGS) was performed. Furthermore, pre- and post-analysis for patients who received asfotase alfa was performed using the Wilcoxon signed-rank test. Results: The study included 19 HPP cases, of whom 68.4% were male. There were five patients with perinatal onset (26.3%), 13 with infantile onset (68.4%), and one with childhood onset (5.3%) of HPP. About 78.9% of patients indicated a family history of HPP; consanguinity was observed in nearly all parents of cases. Bone deformities were observed in all patients, including skull (78.5%), limb (100%), spinal (49.9%), and dental abnormalities (57.9%). Complications such as craniosynostosis (78.5%), nephrocalcinosis (26.3%), kyphoscoliosis (49.9%), and convulsions (26.3%) were also documented, with 4 (21.05%) deaths. Thirteen (68.4%) of our patients received asfotase alfa. All cases tested positive for Conclusion: Our study highlights HPP's diverse phenotypes and genotypes in Saudi Arabia, revealing distinct