Endocrine Abstracts

JOINT1235

Introduction: Hypophosphatasia (HPP) is a rare genetic disorder caused by loss-of-function mutations in ALPL, which encodes tissue-nonspecific alkaline phosphatase (ALP). HPP is classified into six forms according to the onset and severity of manifestations: perinatal lethal, perinatal benign, infantile, childhood, adult, and odontohypophosphatasia. Perinatal and infantile forms have high mortality, making early diagnosis and intervention critical. Enzyme replacement therapy (ERT) with human recombinant tissue-nonspecific ALP (asfotase alfa) became available in Korea since 2016. This study describes the clinical characteristics of Korean HPP patients and presents an 8-year ERT experience in two patients with perinatal lethal and infantile HPP, highlighting their clinical course and long-term outcomes.

Patients and Methods: HPP was suspected in patients with markedly low ALP levels, and the diagnosis was confirmed by mutations in ALPL. We collected information on patients’ demographics, laboratory findings, radiographic features, genetic variants, and clinical courses. Among HPP patients (one perinatal lethal, one perinatal benign, one infantile, two childhood, one odontohypophosphatasia, and two siblings presumed to develop into adult HPP based on family history), six were followed without ERT due to the absence of severe skeletal deformities, motor dysfunction, or pain. Two patients with infantile and perinatal lethal HPP received ERT. 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 8 years.

Outcomes: Radiographic improvements were observed: in the infantile HPP patient, the Rickets Severity Scale (RSS) score decreased from 10 to 7, and the Radiographic Global Impression of Change (RGI-C) score was +2. 3; in the perinatal lethal HPP patient, the RSS improved from 8 to 0, with an RGI-C score of +3. 0. Growth also improved: height standard deviation score (SDS) increased from -6. 37 to -5. 08 (infantile) and from -3. 00 to -1. 84 (perinatal lethal). The perinatal lethal patient had no radiographic signs of rickets after 3 years of ERT. Mechanical ventilation and supplemental oxygen were discontinued after 4. 5 years (infantile) and 2 months (perinatal lethal). Despite a more severe initial condition, the perinatal lethal patient showed greater improvement, emphasizing the importance of early treatment.

Conclusion: HPP should be considered when serum ALP is consistently low. Early diagnosis is important to ensure appropriate monitoring of patients with HPP. In particular, patients with perinatal lethal and infantile HPP should receive prompt treatment to avoid premature mortality and improve long-term prognosis.

Keywords: alkaline phosphatase, ALPL, bone, enzyme replacement therapy, hypophosphatasia