Endocrine Abstracts

JOINT4009

Background: Familial hypocalciuric hypercalcaemia (FHH) type 1 is caused by mutations in the CASR gene which encodes the calcium sensing receptor (CaSR). It is inherited in an autosomal dominant pattern with high penetrance. CaSR is highly expressed in parathyroid glands and kidneys and is an important regulator of calcium homeostasis. Inactivating/loss-of-function mutations in CaSR result in a decreased sensitivity of CaSR to serum calcium, leading to inappropriate PTH release with respect to hypercalcaemia. This PTH effect leads to an increase in renal tubular reabsorption of calcium. The net biochemical effect is of hypercalcaemia, with inappropriately normal or mildly elevated PTH and low urinary calcium. Well described symptoms of hypercalcaemia include nephrocalcinosis, gastrointestinal symptoms and fatigue. Conversely patients with FHH are often asymptomatic and this condition is usually identified incidentally. In terms of management, calcimimetic medications are allosteric agonists at CaSR. By enhancing the effect of extracellular calcium at the CaSR they consequently reduce serum calcium levels. However given the benign natural history of FHH, the necessity of these medications is controversial. Particularly in a paediatric population where safety and efficacy are not well established. We aimed to review symptomatology in our patients with FHH1 to add to the debate of whether treatment is required.

Methods: We retrospectively reviewed cases of patients with FHH1 actively attending our endocrine clinic. Patient demographics, calcium measurements and documented symptoms were collected. Data are mean ± standard deviation unless otherwise stated.

Results: 11 participants were identified over the last ten years. All patients had confirmed CaSR heterozygous mutations. (45%) n = 5 patients from same kindred and remainder (n = 7) were unrelated. Diagnosis was made at age 5. 75 years ± 6. 07 and resulted from an incidental finding of hypercalcaemia in 72% (n = 8) and screening due to family history in 27% (n = 3). Serum calcium at diagnosis 2. 95 mmol/l ± 0. 10. Range of serum calcium over time 2. 66 to 3. 1 mmol/l. The most common symptom reported was constipation in 36% (n = 4). One patient reported polydipsia, all other patients (n = 6) were asymptomatic. All patients had normal renal ultrasound.

Conclusions: The majority of patients with FHH1 attending our service are asymptomatic of hypercalcaemia. Constipation was the only consistently reported symptom and given the prevalence of constipation in a paediatric population, causality from hypercalcaemia alone is unlikely. Given these findings, we have not considered calcimimetic medication for any of our patients. Further prospective studies to correlate calcium concentrations with symptoms is warranted for this paediatric cohort.