Activating mutation of the Calcium sensing receptor as a cause of hypocalcemia

Sulmaaz Qamar; Stephanie Baldeweg

doi:10.1530/endoabs.82.WB4

Introduction: Calcium sensing receptor (CaSR) plays a role in calciotropic processes by regulating parathyroid hormone secretion and urinary calcium excretion. Activating mutation of the CaSR, with heterozygous gain in function, causes autosomal dominant hypocalcaemia 1 (ADH1), a rare disorder with a prevalence of 3.9 per 100,000. Aggressive treatment to normalise serum calcium causes nephrocalcinosis and hypercalcaemia. We present a case of a 27-year-old female with CaSR mutation who developed nephrocalcinosis and brain calcifications.

Case Presentation: Our patient presented aged 11 years with severe hypocalcaemia and undetectable parathyroid hormone (PTH). Genetic testing confirmed the presence of CaSR mutation. She was treated with 2.5 mg alfacalcidol and 500mg calcium supplements daily with calcium levels in the reference range. Nephrocalcinosis was diagnosed a year later. The calcium level was set at a lower range between 1.70-2.10 mmol/l until age 17. A multidisciplinary team meeting was held following transfer to adult endocrine services, and it was decided to use urinary calcium levels as the guide for replacement. At 26 years of age, her urinary calcium showed a rise (see chart) and an Ultrasound of her kidneys showed recurrence of nephrocalcinosis. Bone mineral density was normal. Our patient was using the oral contraceptive pill since menarche aged 12 and developed post-pill amenorrhea aged 26 with a diagnosis of premature ovarian insufficiency (POI) biochemically treated with HRT. At the end of the same year, the patient developed a generalised tonic-clonic seizure treated with anticonvulsant, Imaging showed marked calcification in subcortical white matter, basal ganglia, thalamus, and cerebellum. Her hypocalcaemia is currently managed on alfacalcidol and calcium, monitored by urine calcium.


Year	Calcium(mmol/l)	Adj Ca(mmol/l)	Phosphate(mmol/l)	24h urinary Ca(mmol/24h)	Creatinine(umol/l)	Potassium(mmol/l)	eGFR
2016	1.75	1.78	1.85	6	60	4.5	>90
2018	1.67	1.70	1.43	2.4	69	4.0	>90
2021	2.32	2.24	1.91	8.5	75	4.6	84

Conclusion: This is a rare case of a patient with CaSR mutation developing complications such as nephrocalcinosis, seizures and calcification in several areas of the brain. It is not clear if POI is linked to this condition. We are currently considering firstly non-conventional therapies such as diuretics or recombinant parathyroid hormone to prevent complications and secondly best measure to monitor calcium load.

Endocrine Abstracts

WB4