Modern methods of hypophosphatasia treatment

A.V. Vitebskaya, A.L. Kungurtseva I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow 

Hypophosphatasia (HPP) is an orphan inherited disease caused by a deficiency of tissue-nonspecific alkaline phosphatase (TNAP) due to mutation in the ALPL gene, manifested by rickets-like bone deformities, tooth loss, muscle weakness and febrile seizures. The severity of HPP is variable: depending on the age of manifestation, there are perinatal, infantile, child and adult forms. In previous years, the treatment was purely symptomatic. However, currently, there is the only method of pathogenetic therapy — asfotase alfa (AA) enzyme replacement therapy, which efficacy and safety have been proven in clinical studies. There are also alternative treatment methods including the use of teriparatide and monoclonal antibodies to sclerostin, preclinical studies of gene therapy are being conducted. Bisphosphonate therapy in HPP is contraindicate d. Treatment with AA may be recommended for patients with a confirmed diagnosis of HPP in the presence of skeletal manifestations and child onset. Individual indications have been developed for the administration of AA in the adult form of HPP. The efficacy of AA enzyme replacement therapy is assessed by improving the clinical and radiological manifestations of HPP. The follow-up of patients with HPP includes laboratory and instrumental studies to evaluate the efficacy of therapy and search for ectopic calcifications. A patient with HPP needs consultation by a multidisciplinary specialist.

Keywords: hypophosphatasia, alkaline phosphatase, asphotase alpha, replacement therapy, pathogenetic therapy, multidisciplinary approach.

For citation: Vitebskaya A.V., Kungurtseva A.L. Modern methods of hypophosphatasia treatment. RMJ. 2022;5:36–39.