Long-Term Outcomes of Early Enzyme Replacement Therapy With Asfotase Alfa in Perinatal Benign Hypophosphatasia: Amelioration of Bone Deformities in a Young Child

Hypophosphatasia (HPP) is a congenital skeletal dysplasia. Enzyme replacement therapy (ERT) improves survival and bone mineralization of patients with perinatal severe HPP. However, there are few reports of ERT in patients with perinatal benign HPP, and its long-term efficacy remains unclear. Herein, we report the case of a boy with perinatal benign HPP who was initiated on early ERT with asfotase alpha. The patient was suspected of having HPP because of shortened limbs and deformed long bones on fetal 3D-CT. He was diagnosed with HPP based on clinical manifestations, low serum alkaline phosphatase levels, and <i>ALPL</i> gene variants. At the age of two years and three months, he had muscle weakness and motor developmental delay requiring support to walk, and ERT was initiated. His muscle strength improved immediately, and he could walk independently two months after starting ERT. Shortening and bowed limbs improved, and his body height increased from -3.48 SD (at the age of two years and three months) to -1.71 SD (at the age of nine years and eight months) after starting ERT. Hence, early ERT effectively improves motor development, bone deformity, and short stature in patients with perinatal benign HPP.