Clinical phenotypes of hypophosphatasia due to ALPL gene mutations and the effectiveness of enzyme replacement therapy with asphotase alpha in children

The article provides current information on the clinical forms of hypophosphatasia. The OMIM catalog lists 5 forms of hypophosphatasia: perinatal (lethal), infantile, childhood, adult, and odontohypophosphatasia. The ORPHA portal identifies 6 subtypes of the disorder, including adult, childhood, infantile, perinatal (lethal), and prenatal (benign) hypophosphatasia. M.E. Nunes (2023) identifies 7 forms of hypophosphatasia. International studies have established the pathogenesis, phenotypic variability, and severity of hypophosphatasia. A global consortium provides information on 446 mutation variants of the ALPL gene and 797 genotypes in pediatric and adult patients. The review presents updated diagnostic criteria for hypophosphatasia in children and adults with low alkaline phosphatase activity in the blood. Ten years of experience in 40 countries have proven the safety and efficacy of enzyme replacement therapy with Asfotase Alfa in children with perinatal, infantile, childhood hypophosphatasia, and odontohypophosphatasia. In the Russian Federation, enzyme replacement therapy with Asfotase Alfa for children with hypophosphatasia has been funded by the Circle of Kindness Foundation, established by the Ministry of Health, since 2021.