Diagnosis, treatment, and follow-up of patients with hypophosphatasia.

Introduction: Hypophosphatasia is a rare inherited systemic metabolic disorder, with an estimated prevalence in the severe forms of the disease of 1/100.000-1/300.000, that affects the typical architecture of bone, leading to defective mineralization during growth and remodeling. It is characterized by loss-of-function variants in the ALPL gene, resulting in low activity of tissue-nonspecific alkaline phosphatase. In severe cases, it can be fatal.

Objective: To generate recommendations on the diagnosis, treatment, and follow-up of patients with hypophosphatasia based on available evidence.

Materials and methods: A search for evidence published between 2012 and 2024 was carried out in Medline and Embase. The search was expanded with information from various sources, including official sites of development groups, consensuses, technology evaluations, Google Scholar, clinical experts, and reference lists. The quality of the evidence was evaluated according to the type of document type. A modified Delphi consensus process was carried out with external experts, apart from the development group, it was established an 80% agreement threshold to define the final recommendations.

Results: Sixty-one papers were found in the evidence search. The global quality of the evidence was low. In addition, a consensus was reached on 94 recommendations regarding diagnosis, treatment, and follow-up. Those recommendations were approved by external clinical experts from Colombia, Argentina, Spain, and Mexico.

Conclusions: The recommendations proposed in this document are based on the evidence available to the date the search was carried out, and the judgment of clinical experts. The recommendations on diagnosis, treatment, and follow-up are expected to guide the daily clinical practice for patients with HPP.