L’hypophosphatasie

Abstract

Hypophosphatasia is a rare inherited skeletal disorder caused by loss-of function mutations in the APLP gene that encodes the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). There is a great variability of clinical expression. The presentation varies from a lethal neonatal presentation to mild manifestations in adulthood. In adults clinical manifestations include fractures, with recurrent metatarsal fractures and slowly healing, atypical femoral fractures, dental anomalies, chondrocalcinosis with crystalline arthritis, muscle pain. There is poor recognition of low alkaline phosphatase values. However, this diagnosis is important in order to avoid the use of antiresorptive therapy in case of fracture. The management of hypophosphatasia is provided by a multidisciplinary team, in collaboration with reference centers for rare bone diseases; it includes symptomatic measures and enzymatic replacement therapy (asfotase alfa) is an approved treatment for pediatric-onset hypophphosphatasia now available.