Endocrine Abstracts

Introduction: Inactivating mutations of the calcium sensing receptor (CASR) are associated with familial benign hypercalcaemia (FBH) and neonatal severe hyperparathyroidism whilst activating mutations are associated with autosomal dominant hypocalcaemia (ADH) and Bartter syndrome Type V.

Aims: To highlight the phenotypic and biochemical variability seen with both activating and inactivating mutations of the CaSR.

Methods: To describe clinical presentation and biochemical markers of 5 cases.

Results: Three cases with ADH and activating mutations of the CaSR.

Case 1: Presented aged 11 years with hypocalcaemic tetany following history of muscle cramps for 6 years, hypoparathyroidism and increased urinary calcium excretion. No known family history. Possibility that learning difficulties may be secondary to long term hypocalcaemia.

Case 2: Presented with neonatal convulsions secondary to hypocalcaemia and normal PTH with concurrent Vitamin D deficiency. With correction of Vitamin D deficiency, PTH level is now low. Father, grandmother and aunt are also similarly affected.

Case 3: Presented as an infant with hypocalcaemia with hypoparathyroidism as well as problems with significant hypercalciuria resulting in problems with nephrocalcinosis with no family history. All three cases require small doses of alfacalcidol to remain asymptomatic but hypercalcaemia and nephrocalcinosis remain problematic.

Two cases with FBH

Case 4: Presented as an infant with incidental hypercalcalcaemia with a family history of mother needing a total parathyroidectomy due to hypercalcaemia for ‘hyperparathyroidism’.

Case 5: Presented with hypotonia as an infant and was noted to have hypercalcaemia with variable levels of PTH (between low and normal). No treatment needed in either case.

Conclusion: The case reports illustrate the diversity and variable presentations as well as the importance of gaining a good personal and family history. It also emphasises the difficulties in management and the possible consequences, particularly in ADH. ADH could theoretically respond to treatment with rPTH if hypercalciuria is persistent.