Endocrine Abstracts

Introduction: Familial Hypocalciuric Hypercalcemia (FHH) is a benign autosomal dominant condition caused by an inactivating mutation on the gene coding for the Calcium Sensing Receptor (CASR). CASR plays a role in regulating parathyroid secretion and calcium metabolism. The majority of adults with FHH are asymptomatic. This is a case of three young brothers whose genetic tests shows two mutations in each of their CASR gene leading to hypercalcemia and varying symptoms.

Case: A 20-year-old man was being investigated for a non-epileptic seizure and an incidental finding of a serum calcium 3.21 mmol/l was found. On further questioning, he had been complaining of muscle aches, joint pains and fatigue. Subsequent investigations showed paired PTH 2.1–4.6 nmol/l, PTHrP <0.7, calcium excretion index 0.006 – 0.0006 and 24 h urine calcium of 1.6 mmol/24 h. His sestambi scan revealed no parathyroid adenoma and his DEXA scan showed osteopenia. A detailed family history was obtained indicating his mother had suffered from renal stones secondary to hypercalcemia. His siblings were also tested which revealed two brothers with hypercalcemia. Interestingly, the symptoms vary with his brothers, with one being asymptomatic. Genetic testing in all three have revealed the same two mutations for each brother:

Heterozygous for c.553C>T (p.Arg185X)

Heterozygous for unclassified variant c.1375C>A (p.Gln459Lys)

This second mutation is an unknown variant, which has not been reported in literature. Genetic testing of the parents has shown one altered copy gene in each. First line treatment, Cinacalcet has been used for the symptomatic brothers with one brother showing benefit.

Conclusion: This case illustrates a novel double heterozygous affecting each brother differently. Considering most cases of FHH are asymptomatic, two of the kindred are severely affected as in neonatal hyperparathyroidism. The next step would be to consider a parathyroidectomy to reduce complications.