Endocrine Abstracts

Autosomal Dominant Hypocalcaemia (ADH) type 1 is caused by activating mutations of the calcium-sensing receptor (CaSR) gene. Although a rare condition, the exact prevalence is uncertain as patients are asymptomatic and, historically, were sometimes diagnosed with hypoparathyroidism (HPT) due insensitivity of earlier PTH assays and failure to check urinary calcium. The consequences of an erroneous diagnosis of HPT in patients with ADH can be profound, as treatment with calcium salts or activated vitamin D characteristically result in more severe hypercalciuria and nephrocalcinosis. A 28-year-old female was referred with hypocalcaemia, extreme tiredness and generalised muscle aches that persisted despite correction of hypovitaminosis D. She had no paresthesia symptoms of tetany or muscle spasms, but suffered from intermittent restless legs at night. There was no history of recurrent urinary tract infections or kidney disease. She had a normal childhood with no significant past medical history. There were no significant medical or genetic conditions in the family, except for type II diabetes. She gave birth to a healthy girl 5 years ago with no complications. She had gastric banding for obesity a year ago and recovered well from the surgery with no complications. She is not on regular medications. On examination, she was clinically euthyroid, with positive Chvostek’s but negative Trousseau’s signs. Other systems were unremarkable. Height was 1.69 m. Her kidney ultrasound showed no renal calculi. Genetic analysis of the patient identified a heterozygous autosomal dominant CASR variant: c.2497G>T (p.Val833Phe) diagnosing her with Autosomal Dominant Hypocalcaemia Type 1 (ADH). This gene variant has not been identified in the gnomAD population database yet. In conclusion, hypocalcaemia needs to be investigated as we now have better assays to detect low normal PTH levels. Misdiagnosing ADH type 1 with hypocalcaemia or HPT increases the risk of nephrocalcinosis and hypercalciuria in those patients.