Endocrine Abstracts

Case history: A 16 month old boy was referred to Community Paediatrics with developmental delay. Bloods taken as part of a developmental delay screen, revealed a raised calcium, with an inappropriately normal parathyroid hormone (PTH) and a normal vitamin D. There was no family history of hypercalcaemia. Blood tests in the boy’s mother and grandmother also showed hypercalcaemia.

Investigations: Calcium was raised at 3.46 mmol/l. A urinary calcium creatinine ratio was low at 0.0045. A renal ultrasound showed no evidence of renal calcinosis. This was similarly the case in his mother and grandmother. Genetic testing showed a heterozygous Calcium Sensing Receptor (CaSR) mutation, c.554G>A p.(Arg185Gln), confirming the diagnosis of Familial Hypocalciuric Hypercalcaemia (FHH) in all 3 relatives. Interestingly, the severity of hypercalcaemia increased down the generations, with the boy having a higher calcium level than his mother and grandmother, respectively.

Results and treatment: FHH is typically a benign condition, with no specific treatment required. Patients with FHH typically have an excellent prognosis. It is important to differentiate from primary hyperparathyroidism, the latter of which may require surgery.

Conclusions and points for discussion: FHH is rare, with a prevalence of 1 in 78 000¹. Patients are not at increased risk of renal calculi or osteoporosis. The main differential is the much more common condition, primary hyperparathyroidism. There are several subtypes of FHH. The most common, occurring in approximately 65% of cases², FHH type 1, is due to a mutation in the CaSR gene, located on chromosome 3. This is responsible for making CaSR protein, which monitors and regulates blood calcium levels, and is found predominantly in the parathyroid glands and kidneys. CaSR mutations results in reduced sensitivity of the parathyroid gland to high calcium levels, resulting in hypercalcaemia as well as ongoing raised PTH levels. Patients with FHH typically have an excellent prognosis. FHH is not generally associated with developmental delay, the exception to this being FHH type 3. In this case, another microduplication was found, known to be associated with developmental delay.

References: 1. Brixen K. Familial benign hypocalciuric hypercalcaemia – an update. Endocrine Abstracts 2009; 16:19

2. Pearse SH et al. Calcium-sensing receptor mutations in familial benign hypercalcaemia and neonatal hyperparathyroidism. Journal of Clinical Investigation 1995; 96(6):2683–92