Context: Persistent hypercalciuria, with the attendant risk of nephrocalcinosis and eventual renal failure, is common in hypoparathyroid patients, especially those with activating mutations of the calcium-sensing receptor (CASR) gene, being treated with oral calcium and calcitriol. Treatment with replacement parathyroid hormone (PTH) may be warranted although this has yet to be evaluated in children.

Objectives: To identify the cause of the disorder in a young hypocalcemic patient. To assess the efficacy of treatment of the patient with recombinant human PTH (1-34). Subject: An infant presenting with hypocalcemia at 3 weeks of age.

Methods: CASR gene mutation analysis was performed on genomic DNA of the proband and family members. The patient was treated with twice-daily administration of recombinant human PTH (1-34) over a 17-month period.

Results: The proband was heterozygous for a de novo novel missense mutation (L727Q), on the border between transmembrane helix 4 and intracellular loop 2 of the CASR. When transiently expressed in a human kidney (HEK293) cell line, the mutant receptor demonstrated a significant leftward shift in the extracellular calcium/intracellular signaling dose-response curve vs. that for the wild-type receptor [EC₅₀; mutant, 2.59 ± 0.11 mM (mean±SE) vs. wild-type, 3.78 ± 0.12 mM, P < 0.001]. During treatment with PTH (1-34), the patient had no further serious hypocalcemic episodes and his urinary calcium excretion declined remarkably.

Conclusion: PTH should be evaluated further as a treatment of autosomal dominant hypocalcemia in young patients.