Bone Abstracts

Background: 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).

Presenting Problem: HPP should be considered when serum ALP is continuously low. 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.

Clinical management: 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 dose of 2 mg/kg three times weekly subcutaneously. All patients survived and the radiographic findings, laboratory findings, developmental milestones and respiratory function were improved. Injection site reactions were the most frequent adverse events, however, no serious adverse events were noted. Our results add support to the safety and efficacy of treatment with asfotase alfa for HPP patients.

Discussion: Accurate diagnosis and prompt treatment play an important role for avoiding preventable morbidity and premature mortality in patients with HPP. A persistently low ALP level in patients with unspecified diagnoses could be a key to diagnose HPP. Premature exfoliation of primary teeth may be the first manifestation of HPP and the general dental practitioner plays an important role in recognizing dental anomalies and referring patients at an appropriate time. Our screening of HPP planned by age/sex-specific reference ranges of ALP and collaborative work with dental doctors could prompt physicians to investigate for undiagnosed HPP. This is imperative to ensuring early diagnosis and good quality patient care.

Disclosure: The authors declared no competing interests.