Endocrine Abstracts

Background: The calcium sensing receptor (CaSR) plays a pivotal role in systemic calcium metabolism by regulating parathyroid hormone (PTH) secretion and urinary calcium excretion. Autosomal dominant hypocalcaemia type 1 (ADH1) is a disorder of extracellular calcium homeostasis caused by activating germline gain-of-function mutations of the CaSR.

Case: A 13-year-old girl was referred from primary care with hypocalcaemia. She was under CAMHS for eating disorder and anxiety. Baseline serum adjusted calcium was (1.81 mmol/l). This was felt to be nutritional due to low vitamin D. She was started on vitamin D and calcium supplements. Repeat bloods after two weeks showed normal vitamin D (67 nmol/l) and magnesium (0.7 mmol/l), low calcium (1.86 mmol/l) and inappropriately “normal” PTH (1.5 pmol/l). Renal function was normal and urinary Ca/creatinine ratio was 0.5 mmol/ mmol(range <0.6). She was born at 30/40 gestation due to maternal jaundice and is one of identical twins. There was no reported history of neonatal hypocalcaemia, her iCa on the blood gases was low normal (1.06 mmol/l) during her NICU admission. She had been fit and well until recently – but after more questioning her mother reported stridor during sleep. On examination, she had positive Chvostek sign. Calcium levels improved on supplements (Ca, Mg, alfacalcidol) but urinary calcium/creatinine ratio increased to 0.9. She had a normal renal and thyroid ultrasound. CT brain showed bilateral basal ganglia calcifications. Genetic testing showed heterozygosity for a CASR variant, confirming ADH1. Her twin sister was tested and had the same diagnosis. She was asymptomatic but also had mild hypocalcaemia.

Discussion: Patients with ADH1 can have no (asymptomatic), mild or severe symptoms (in similar proportions) and there is lack of phenotype correlation. Although this could explain the different presentation in these identical twins, it is also possible that the higher levels of anxiety in our index case and hyperventilation induced alkalosis exacerbated the existing hypocalcaemia. Although recombinant PTH (injectable or via subcutaneous infusion) has been used to treat patients where standard therapy with Ca and alfacalcidol/calcitriol supplementation is not practical or ineffective, novel therapies using allosteric modulators (calcilytics) are showing very promising results in trials.