Severe Hypercalcemia Associated With Perinatal Hypophosphatasia While Receiving Enzyme Replacement Therapy

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Hypophosphatasia (HPP) is a rare genetic disorder caused by pathogenic variants in the ALPL gene, leading to defective bone mineralization due to reduced tissue-nonspecific alkaline phosphatase (TNSALP) activity.
• Hypercalcemia is a significant complication, particularly in perinatal and infantile forms of HPP, and enzyme replacement therapy with asfotase alfa (AA) is used for management.

Observation:

• A patient with perinatal HPP developed severe hypercalcemia while undergoing treatment with asfotase alfa (AA).
• Initial management included intravenous fluids, dietary calcium restriction, and optimizing the AA dose, but hypercalcemia persisted, necessitating hospitalization.
• Adjunct therapy with calcitonin was initiated, leading to normalization of calcium levels without recurrence.

Findings:

• Calcitonin administration, alongside restricted calcium intake and maximal asfotase alfa dosing, proved effective in managing severe hypercalcemia in this infant with HPP.
• The patient was gradually weaned off calcitonin and calcium restrictions over 8 months, maintaining normal calcium levels.
• This case demonstrates the successful use of calcitonin as an adjunct treatment for severe hypercalcemia in infants with HPP.

Implications:

• Vigilant monitoring of calcium levels and dietary intake is crucial for infants diagnosed with HPP, especially those receiving enzyme replacement therapy.
• While not a standard long-term treatment, calcitonin can be an effective adjunct therapy for managing severe hypercalcemia in HPP.
• This case expands therapeutic options for managing complex hypercalcemia associated with HPP in pediatric patients.