Continuous subcutaneous recombinant PTH(1-34) infusion improves serum calcium and phosphate homeostasis in children with autosomal dominant hypocalcemia type 1 refractory to standard-of-care treatment

OBJECTIVE: Autosomal dominant hypocalcemia type 1 (ADH1) results from activating CASR variants, causing parathyroid hormone (PTH) suppression and abnormal renal calcium handling. Management is challenging, as hypoparathyroidism is associated with inappropriate renal calcium wasting, leading to hypercalciuria, nephrocalcinosis, and renal impairment. We evaluated long-term outcomes of continuous subcutaneous PTH(1-34) infusion (CSPI) in children with ADH1 refractory to standard of care therapy (SOC). DESIGN: Single-center observational study. METHODS: Five children with genetically confirmed ADH1 were treated with CSPI between 2012 and 2017 and followed for up to 11 years. Clinical outcomes, biochemical parameters, and renal findings were assessed under SOC and CSPI. Serum calcium, phosphate (standard deviation score, SDS), magnesium, alkaline phosphatase, eGFR, urinary calcium/creatinine ratio (relative to the age-specific 95th percentile), and fractional calcium excretion (FECa) were analyzed using linear mixed-effects models. RESULTS: Hypocalcemic seizures and emergency visits decreased, growth was appropriate, and no treatment-related adverse events occurred over a median 7-year follow-up. CSPI was associated with higher serum calcium (P < .001) and lower serum phosphate (P < .001). Urinary calcium/creatinine ratios, expressed relative to the age-specific 95th percentile, were lower under CSPI (P < .001). FECa was approximately 8% lower under CSPI (P = .014), suggesting improved renal calcium handling. Renal function remained stable despite progression of nephrocalcinosis in 4/5 patients. CONCLUSION: SPI appears to be a safe and effective long-term treatment in pediatric ADH1, improving mineral homeostasis and renal calcium handling. Prospective multicenter studies are needed to assess long-term skeletal outcomes and optimize dosing strategies.