Case Report: Palopegteriparatide as a novel therapeutic option in pediatric autosomal dominant hypocalcemia type 1.

INTRODUCTION

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare genetic disorder caused by gain-of-function variants in the CASR gene, leading to suppressed parathyroid hormone (PTH) secretion, hypocalcemia, hyperphosphatemia, hypomagnesemia and hypercalciuria. Evidence on the use of long-acting PTH analogs in pediatric ADH1 remains scarce. This report describes a boy with a de novo heterozygous activating CASR variant and highlights the therapeutic response to palopegteriparatide.

CASE PRESENTATION: A 16-year-old boy presented with hypocalcemia, recurrent tetany, seizures, hypercalciuria, nephrocalcinosis, basal ganglia calcifications, and early-onset cataracts. He had been diagnosed with congenital hypoparathyroidism at 6 weeks of age. A heterozygous CASR variant [c.2504C>A; p.(Ala835Asp)] causing ADH1 was identified. Despite long-term therapy with alfacalcidol, calcium, and magnesium supplements, symptoms persisted and biochemical control remained poor, with pronounced hyperphosphatemia and an elevated calcium-phosphate product.

INTERVENTION AND OUTCOMES: Owing to inadequate disease control on Standard-of-Care, off-label treatment with palopegteriparatide was initiated. The dose was adjusted to alleviate neuromuscular symptoms while reducing calcium-phosphate product. The patient subsequently reported complete resolution of tetany with improved biochemical stability, reduced phosphate levels, and a lower calcium-phosphate product. At the final maintenance dose, both alfacalcidol and calcium supplementation were successfully discontinued.

CONCLUSION

This case demonstrates that palopegteriparatide may be a valuable therapeutic option in pediatric patients with ADH1 when conventional therapy fails to provide adequate control and while targeted therapies directed at the mutated CASR are not yet available. Carefully titrated PTH-based therapy can improve symptoms and mineral homeostasis, highlighting the need for further studies on its long-term safety and efficacy in children.