Endocrine Abstracts

Introduction: Autosomal dominant hypocalcemia (ADH) is a rare condition, caused by activating mutations in the calcium-sensing receptor (CASR) gene. Affected individuals have hypocalcemia with inappropriately low parathyroid hormone (PTH) levels.

Case report: A 50-year-old woman, asymptomatic, was referred to our Endocrinology department for investigation of hypocalcemia detected in routine blood analysis (serum corrected calcium was 7.4 mg/dl – normal: 8.6–10.2). There was also hyperphosphatemia (5.4 mg/dl – normal: 2.4–5.1) and abnormally low PTH (9.9 pg/ml – normal: 14–72).

Her past medical history was irrelevant except for depression in the past. She denied taking any prescription. There was no history of neck surgery/radiation or known family history of hypocalcemia. Thyroid function, morning serum cortisol and 24-h urinary cortisol, fasting glucose, 25-hydroxyvitamin D, renal function, serum magnesium, sodium and potassium were normal. Auto-antibodies against thyroid, parathyroid and adrenal gland were negative. Brain computed tomography identified basal ganglia calcifications. A few first-degree relatives (74-year-old mother, sisters aged 44 and 49, and 30-year-old son) were also screened for hypocalcemia. The mother and the younger sister, both asymptomatic, had hypocalcemia and inappropriately low PTH. The mother also presented basal ganglia calcifications. The son and the older sister had normal calcium levels. Genetic analysis identified a novel heterozygous CASR variant: c.2269G>A (p.Glu757Lys) in the proband, her mother and younger sister whereas it was not identified in the son and older sister. Affected individuals started calcium replacement aiming to a low-normal calcium level (8–8.5 mg/dl).

Conclusion: The co-segregation of the novel CASR variant with the hypocalcemic phenotype in the family favor its pathogenic role. Clinical investigation and diagnosis of this condition can be challenging, but treatment and long-term monitoring are essential to prevent complications, such as neurological.