Treatment of hypophosphatasia

Abstract

ypophosphatasia is a systemic metabolic disorder due to genetically determined deficient activity of the tissue non-specific alkaline phosphatase (TNAP). The phenotypic presentation is characterized by a wide spectrum of clinical manifestations regarding both, affected body systems and organs as well as the severity of associated deficits. Appropriate treatment strategies thus have to be multimodal in order to cover individual disease manifestation. For patients with disease onset before adulthood, enzyme replacement therapy with asfotase alfa is approved in Europe to treat the bone manifestations of the disease. Available data from clinical trials as well as real-word evidence confirm encouraging results of this treatment in severely affected children with substantial improvement regarding radiographic and functional outcome parameters as well as overall survival. In adult patients with disease manifestation pursuant to the label, published results also report substantial amelioration of disease-specific deficits along with functional improvements. Meanwhile, there is are also data supporting the safety and efficacy of long-term treatment with asfotase alfa over several years. While inflammatory muskuloskeletal pain - seemingly the most prevalent clinical manifestation along with exhaustion - can transiently be mitigated with on-demand NSARs, essential treatment options to causatively overcome that issue are still lacking. Accordingly, maintenance of musculoskeletal health and functionality requires sustained supportive treatment including physiotherapy and individually adjusted technical orthopedic support. The use and potential clinical impact of phosphate and vitamin B6 on the course of the disease requires further investigation. Current data regarding the use of bone-targeted compounds established for osteoporosis is critical in terms of antiresorptive, while osteoanabolic treatment strategies appear feasible. Considering further organ manifestation including orodental, gastrointestinal and neurological symptoms etc., the entirety of therapeutic measures should be coordinated among a multidisciplinary team and overlooked at an experienced center, while individual tasks can preferably be accomplished at local facilities near the patient’s home.