Six-year clinical outcomes of enzyme replacement therapy for perinatal lethal and infantile hypophosphatasia in Korea: Two case reports

Abstract

Introduction: Hypophosphatasia (HPP) is a genetic disease caused by loss-of-function mutations in ALPL, which encodes tissue-nonspecific alkaline phosphatase (ALP). Early diagnosis and treatment of perinatal and infantile HPP are important because of their high mortality rates. Enzyme replacement therapy (ERT) using human recombinant tissue-nonspecific ALP asfotase alfa was introduced in Korea in 2016. We report the first experience of ERT over 6 years for perinatal lethal and infantile HPP in Korea. Patient concerns: The first patient was a 6-week-old Korean boy with a failure to thrive. The second patient was an 8-day-old Korean-Uzbek body with generalized tonic-clonic seizure with cyanosis. Diagnoses: HPP was suspected in both patients because of the very low level of ALP activity and rachitic findings on radiographs, and the disease was confirmed by Sanger sequencing of the ALPL gene. Intervention: The first patient with infantile HPP started ERT at 21 months of age and the second patient with perinatal HPP started ERT at 30 days of age. Both patients received asfotase alfa (2 mg/kg 3 times per week subcutaneously, adjusted to 3 mg/kg 3 times per week if required) for 6 years. Outcomes: After 6 years of ERT, radiographic findings and growth standard deviation scores improved in both patients. The second patient showed no evidence of rickets after 3 years of ERT. Mechanical respiratory support and supplemental oxygen were not required after 4.5 years of treatment in the first patient and at 2 months after treatment in the second patient. Conclusion: Among the 2 patients, the patient who started ERT early had a much better prognosis despite a more severe initial clinical presentation. Our results suggest that early diagnosis and prompt treatment play an important role in improving long-term prognosis and avoiding morbidity and premature mortality in patients with perinatal and infantile HPP.