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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., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Mutations of phosphatidylinositol glycan biosynthesis class T ( PIGT ), which encodes a subunit of the glycosylphosphatidylinositol (GPI) transamidase complex, can lead to multiple anomalies, including seizures, intellectual disabilities, facial dysmorphism, and various congenital malformations. We performed whole-exome sequencing in a patient with seizures, intellectual disabilities, truncal ataxia, facial dysmorphism, and persistent hypophosphatasia without rickets or bone mineralization defects, and identified two heterozygous mutations in PIGT , c.250G>T (p.Glu84*) and c.1582G>A (p.Val528Met). GPI-linked protein analyses found no abnormalities. Although the patient's hypophosphatasia persists, no skeletal, urological, or dental abnormalities were found. The seizures disappeared after administering antiepileptic drugs. PIGT mutations should be considered in patients with multiple congenital symptoms and persistent hypophosphatasia., (© 2021 by the Association of Clinical Scientists, Inc.)