Perinatal hypophosphatasia refractory to asfotase alfa with neutralizing antibodies that affected bone...

Hypophosphatasia (HPP) is a rare osteometabolic disease. Enzyme replacement therapy (ERT) for HPP was approved in 2015 and has significantly improved the survival and quality of life of patients. Poor responses to ERT have been reported; however, detailed information is limited. We encountered a case of severe perinatal HPP refractory to ERT with neutralizing antibody (NAb) expression that possibly affected bone mineralization. Asfotase alfa (AA) (6 mg/kg/wk) was initiated 2 mo after birth and resulted in complete resolution of rickets by age 7 mo. However, rickets recurred at age 18 mo without any other identifiable cause than NAbs detected. The AA dose was increased to 9 mg/kg/wk based on the United States prescribing guidelines when the patient was age 3 yr. By ages 4 yr and 8 yr, rickets in the upper limbs and lower limbs, respectively, had nearly disappeared. NAbs were not detected at age 6 yr. We reduced the AA dose (6 mg/kg/wk) at age 8 yr. Rickets recurrence was not observed. Changes in bone mineralization corresponded to NAb expression, suggesting that NAbs may have influenced the therapeutic effect. The optimal AA dose may vary based on clinical findings and the NAb status.