The patient exhibited low serum
alkaline phosphatase (60 U/L; age-matched reference range, 520-1,580) in a routine laboratory test at birth. Further examinations revealed skeletal demineralization and rachitic changes, as well as elevated levels of serum
calcium (2.80 mmol/L; reference range, 2.25-2.75 mmol/L) and ionic
phosphate (3.17 mmol/L; reference range, 1.62-2.48 mmol/L), which are typical features in patients with
hypophosphatasia. Sequencing analysis of the tissue-nonspecific
alkaline phosphatase (TNSALP) gene identified two pathogenic mutations: c.406C>T, p.Arg136Cys and c.979T>C, p.Phe327Leu. Thus, the patient was diagnosed with
hypophosphatasia. At the age of 37 days, she began
enzyme replacement therapy using asfotase alpha at the standard dose of 6 mg/kg/week. Initial
therapy from the age of 37 days to the age of 58 days substantially improved
rickets signs in the patient; it also provided immediate normalization of serum
calcium and ionic
phosphate levels. However, serum ionic
phosphate returned to a high level (2.72 mmol/L), which was presumed to be a side effect of asfotase alpha. Thus, the patient's
asfotase alfa treatment was reduced to 2 mg/kg/week, which allowed her to maintain normal or near normal skeletal features thereafter, along with lowered serum ionic
phosphate levels. Because the patient exhibited slight distal metaphyseal demineralization in the knee at the age of 2 years and 6 months, her
asfotase alfa treatment was increased to 2.4 mg/kg/week. No signs of deterioration in bone mineralization were observed thereafter. At the age of 3 years, the patient's motor and psychological development both appeared normal, compared with children of similar age.
Conclusion: