Endocrine Abstracts

Hereditary hypercalcaemia can be a diagnostic challenge. We present a family with autosomal dominant hypercalcaemia that illustrates this. A 48-year-old man was referred with asymptomatic long standing hypercalcaemia (2.8–3.04 mmol/l), with plasma PTH levels between 45 and 48 ng/l (normal 15–65), and a high urinary calcium excretion, (24 h calcium collection 10.4 mmol/l (2.5–7.5), with high calcium excretion indexes) all consistent with primary hyperparathyroidism. His mother had been referred to a different hospital with hypercalcaemia, and biochemistry consistent with primary hyperparathyroidism. Isotope scan had confirmed a parathyroid adenoma, and calcium levels normalised after parathyroidectomy from >3 to 2.56 mmol/l, with histology confirming an adenoma. Parathyroid uptake scan in our male patient was normal. Screening of his son and daughter confirmed both having hypercalcaemia (2.9–3.0 mmol/l), PTH levels 30–45 ng/l, and urinary calcium excretion indexes 12–18 (< 22 consistent with familial hypocalciuric hypercalcaemia FHH).

The father had genetic testing which confirmed a C to T nucleotide substitution at codon 15 of AP2S1 (adaptor-related protein complex two, sigma one subunit), c.43C>T. This results in replacement of the amino acid arginine with cysteine (p.Arg15Cys) and confirmed FHH type three.

FHH has autosomal dominant trait with high penetrance, and is characterized by elevated serum calcium and is usually asymptomatic. Three types have been characterised. Type one and type two have mutations in the CASR and GNA11 gene respectively, type three FHH is due to a mutation in AP2S1.

It is important to note that father and children had differing phenotypes with father having a high and children a low calcium excretion index. This case highlights the importance of taking a detailed family history, along with biochemical assessments and genetic analyses of close family in patients with hypercalcaemia.