한국 영아형 저인산증 환자들에서 asfotase alfa 치료의 효과와 부작용에 대한 첫 임상적 경험에 대한 보고
First clinical experience of treatment with asfotase alfa for patients with infantile hypophosphatasia in Korea
Abstract
Hypophosphatasia (HPP) is a rare skeletal disease characterized by defective bone and teeth mineralization and the deficiency of tissue non-specific alkaline phosphatase activity. This disorder is caused by mutations in the ALPL gene, which encodes TNAP. The clinical presentation of HPP varies greatly, ranging from stillbirth without bone mineralization (perinatal form) to findings in later life, such as delayed walking, short stature, skeletal deformities, bone pain, and pathologic fractures (childhood and adult form). The diagnosis is based on clinical examination, radiologic findings, biochemical parameters of reduced ALP activity, elevated serum and urine levels of TNAP substrates, and molecular analysis of the ALPL gene. The prognosis for the infantile form is poor, with approximately 50% of patients dying within the first year of life from respiratory failure. Asfotase alfa, a bone-targeted, recombinant TNAP, has recently been developed to treat HPP complications. We describe the clinical features, biochemical findings, molecular analysis, and first clinical experience of treatment with asfotase alfa in patients with infantile HPP in Korea. Patients received asfotase alfa with 2 mg/kg three times weekly subcutaneously. All patients survived and the radiographic findings, laboratory findings, and respiratory function were improved. No serious adverse events were noted except injection site reactions. Our results add support to the safety and efficacy of treatment with asfotase alfa for HPP patients. Accurate diagnosis and prompt treatment play an important role for avoiding preventable morbidity and premature mortality in patients with HPP.