Objectives: Autosomal Dominant Hypocalcaemia (ADH) is due to gain-of-function mutations of the CASR resulting in constitutive activation of the GPCR Calcium Sensing Receptor (CaSR) leading to hypercalciuric hypocalcaemia, hypoparathyroidism and occasionally Bartter syndrome type V. Patients usually present with hypocalcaemic seizures at young age. Conventional treatment is with Alfacalcidol and Calcium or PTH injections. We describe a series of five patients with ADH in whom stabilization of calcium concentrations could not be achieved with conventional treatment and in whom continuous subcutaneous PTH infusion (CSPI) using insulin pumps was started.
Methods and results: CaSR mutations were P.Thr828Asn, not previously described, and the previously described p.Ala843Glu, p.Tyr829Cys, p.Phe821Leu. Patients presented with hypocalcaemic seizures or tetany in the first few weeks of life. Additional features were bilateral cataracts, hypomagnesaemia, Bartter type V. One patient had nephrocalcinosis before CSPI. Age at start of CSPI was 3 weeks, 6 weeks, 6 months, 6 years and 20 years. Medtronic and Omnipod patch pumps were used to deliver diluted PTH(1-34). Treatment was started in an inpatient setting. Duration of treatment is currently 13 years. PTH requirement was 0.21, 0.13, 0.15, 0.5 and 3 mcg/kg per day. Four patients required Magnesium supplementation. All patients received Cholecalciferol. Calcium concentration stabilised and patients continue to require weekly or bi-weekly blood tests. Number of admissions significantly reduced during CSPI. Seizures stopped in all patients on CSPI. Current calcium concentrations range from 1.75 to 2.15 mmol/l. Current urine Calcium/creat ratios range from 1.2 to 2.5 mol/mol. Nephrocalcinosis has remained stable. One patient stopped pump treatment temporarily due to instable calcium concentrations.
Conclusion: We describe continuous subcutaneous PTH infusion as a suitable treatment for ADH that cannot be controlled conventionally. We also describe a new CaSR mutation resulting in ADH and cataracts, which is also a feature of the mouse model for ADH. Cataracts have since been found in some patients with ADH. Longer follow up is required to assess whether continuous sc PTH treatment delays the progression of nephrocalcinosis.
22 - 24 Nov 2017
British Society for Paediatric Endocrinology and Diabetes