Hypophosphatasia: A Rare Disorder

Kiran Panesar, BPharmS (Hons), MRPharmS, RPh, CPh


US Pharmacist. 2017;42(5):HS-27-31. 

In This Article

Abstract and Introduction


Hypophosphatasia is a rare genetic metabolic disorder caused by mutations in the tissue nonspecific alkaline phosphatase gene (ALPL) that lead to defective mineralization of the bones and/or teeth. Hypophosphatasia shares many common clinical features with other skeletal diseases such as osteoporosis, but it is distinctively associated with the presence of low serum and bone alkaline phosphatase. The severity of the disease varies widely, and in some cases patients with the mild form remain undiagnosed. Treatment is largely supportive; until 2015 there was no specific medical therapy for the management of patients with hypophosphatasia. Asfostase alfa is a recombinant, bone-targeted, human tissue nonspecific alkaline phosphatase (TNSALP) that has been used successfully to treat hypophosphatasia and is currently FDA-approved for the treatment of the perinatal/infantile- and juvenile-onset forms.


Hypophosphatasia is a rare autosomal dominant or recessive metabolic disorder caused by mutations in the alkaline phosphatase (ALPL) gene.[1] It was first detected by Rathbun in 1948 and is caused by mutations in the liver/bone/kidney alkaline phosphatase gene–encoding tissue nonspecific alkaline phosphatase (TNSALP).[2] To date, over 200 different mutations in ALPL have been identified.[1,3] The inherited disorder results in defective mineralization of bones and/or teeth in the presence of low serum and bone alkaline phosphatase activity.[2,4] The disease severity varies widely, with severe forms usually manifesting during the perinatal and/or infantile periods; mild forms are sometimes diagnosed in adulthood or remain undiagnosed.[1]