Expert Delphi consensus on the diagnosis and management of Hypophosphatasia in the Gulf Cooperation Council region

Abstract Background Hypophosphatasia (HPP) is a rare, genetic, hereditary, multisystem disorder caused by pathogenic mutations in the ALPL gene that lead to reduced or absent activity of the tissue-nonspecific alkaline phosphatase (TNSALP) enzyme. Its variable age-dependent presentation makes diagnosis challenging, often leading to underdiagnosis or misdiagnosis due to the lack of formal guidelines. This consensus aimed to define the etiology, diagnosis, management, healthcare barriers, and future directions for HPP in the Gulf Cooperation Council (GCC). Methods A modified Delphi consensus approach was employed through two rounds of evaluation by 11 healthcare professionals (HCPs) across the GCC region. Statements were evaluated using a five-point Likert scale, and consensus was defined as ≥ 75% agreement. Results A consensus was reached on 31 statements, emphasizing a comprehensive diagnostic approach that combines clinical assessment, biochemical markers, imaging, and patient-reported outcome measures (PROMs). Recommendations included individualized management, incorporating enzyme replacement therapy (ERT), supportive therapies, and psychosocial care. Region-specific challenges in the GCC include limited physician awareness that delays the referral pathway, restricted diagnostic access, insurance barriers and lack of access to treatment except in few centres. To overcome the challenges, the panel recommended establishing standardized diagnostic criteria and creating specialized centers of excellence with multidisciplinary teams across the GCC. Conclusion The statements establish a definitive consensus model for the diagnosis and management of HPP in the GCC across various age groups. This model is poised to effectively guide clinical practice for all patients with HPP.