Palopegteriparatide resolves tetany, improves mineral homeostasis in pediatric autosomal dominant hypocalcemia type 1
Background
Autosomal dominant hypocalcemia type 1 (ADH1) is a rare genetic disorder caused by gain-of-function variants in the CASR gene, leading to overactive calcium-sensing receptors. This results in suppressed parathyroid hormone (PTH) secretion, causing hypocalcemia, hyperphosphatemia, and hypercalciuria. Current standard-of-care, involving alfacalcidol, calcium, and magnesium supplements, often fails to achieve adequate biochemical control and symptom relief, particularly in pediatric patients. There is a significant clinical gap for effective, targeted therapies that can restore mineral homeostasis without exacerbating complications like nephrocalcinosis, making long-acting PTH analogs a promising area of investigation.
Study Design
This case report describes a 16-year-old boy diagnosed with congenital hypoparathyroidism at 6 weeks, later confirmed as ADH1 due to a de novo heterozygous CASR variant [c.2504C>A; p.(Ala835Asp)]. Despite long-term therapy with alfacalcidol, calcium, and magnesium supplements, he experienced persistent symptoms including recurrent tetany and seizures, alongside poor biochemical control characterized by pronounced hyperphosphatemia and an elevated calcium-phosphate product. Off-label treatment with palopegteriparatide was initiated, with the dose carefully adjusted to alleviate neuromuscular symptoms and reduce the calcium-phosphate product. The patient's response was monitored for symptom resolution and biochemical stability.
Results
Following the initiation of palopegteriparatide therapy, the patient reported complete resolution of recurrent tetany. Biochemical analysis demonstrated improved stability, with a notable reduction in phosphate levels and a lower calcium-phosphate product. This improvement allowed for a significant de-escalation of his previous treatment regimen. > At the final maintenance dose of palopegteriparatide, both alfacalcidol and calcium supplementation were successfully discontinued, indicating a profound positive shift in mineral homeostasis. The patient's clinical picture, including the resolution of severe neuromuscular symptoms and normalization of key biochemical markers, highlights the efficacy of this PTH-based approach in a challenging case of refractory ADH1.
Key Findings
- Palopegteriparatide resolved recurrent tetany in a 16-year-old boy with refractory ADH1.
- Treatment improved biochemical stability, reducing phosphate levels and calcium-phosphate product.
- Patient successfully discontinued alfacalcidol and calcium supplementation.
- Palopegteriparatide offers a potential therapeutic option for pediatric ADH1 unresponsive to standard care.
Why It Matters
This case report suggests that palopegteriparatide may offer a valuable therapeutic option for pediatric patients with ADH1 who do not respond adequately to conventional therapy. For biohackers and clinicians, this highlights the potential of PTH-based therapies to restore mineral homeostasis in conditions of PTH deficiency or dysregulation, even when the underlying cause is a gain-of-function receptor mutation. Carefully titrated PTH-based therapy can improve symptoms and mineral homeostasis, potentially reducing the need for multiple supplements and mitigating long-term complications. While this is an off-label use, it provides a crucial proof-of-concept for a targeted approach when specific CASR modulators are unavailable, paving the way for future studies on its broader applicability and long-term safety.
palopegteriparatide
hypocalcemia
hypoparathyroidism
adh1
casr
pediatric