Department of Public Health Administration, Asan City Health Center, Asan, Korea.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Medicine (Baltimore). 2023 Feb 10;102(6):e32800. doi: 10.1097/MD.0000000000032800.
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.
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.
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.
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.
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.
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.
低磷酸酯酶症（HPP）是一种由 ALPL 基因失活突变引起的遗传性疾病，该基因编码组织非特异性碱性磷酸酶（ALP）。由于围产期和婴儿期 HPP 的死亡率较高，因此早期诊断和治疗非常重要。2016 年，韩国开始使用人重组组织非特异性 ALP 酶替代疗法（ERT）治疗阿法特酶。我们报告了韩国首例使用 ERT 治疗围产期致死性和婴儿期 HPP 的 6 年经验。
第一个患者是一名 6 周大的韩国男孩，生长发育不良。第二个患者是一名 8 天大的韩国乌兹别克斯坦婴儿，伴有全身强直阵挛性发作伴发绀。
两名患者均因 ALP 活性极低和 X 线表现佝偻病样改变而怀疑患有 HPP，并通过 ALPL 基因 Sanger 测序确诊。
第一个患有婴儿期 HPP 的患者在 21 个月大时开始接受 ERT，第二个患有围产期 HPP 的患者在 30 天大时开始接受 ERT。两名患者均接受阿法特酶（2mg/kg，每周 3 次皮下注射，如果需要，调整为 3mg/kg，每周 3 次）治疗 6 年。
经过 6 年的 ERT，两名患者的 X 线表现和生长标准偏差评分均有所改善。第二个患者在接受 ERT 3 年后无佝偻病表现。第一个患者在治疗 4.5 年后和第二个患者在治疗 2 个月后无需机械通气和补充氧气。
在这两名患者中，尽管初始临床表现更严重，但早期开始 ERT 的患者预后要好得多。我们的结果表明，早期诊断和及时治疗在改善围产期和婴儿期 HPP 患者的长期预后、避免发病率和过早死亡方面发挥着重要作用。
