(7.07) An Unusual Case of Autosomal Dominant Hypocalcemia with Bartter Syndrome Presenting in Adulthood

Gain-of-function mutations of the calcium-sensing receptor (CaSR) gene have been identified in patients with familial or sporadic autosomal dominant hypocalcemia (ADH). It is a rare genetic disorder characterized by hypocalcemia with low parathyroid hormone (PTH) levels due to decreased serum calcium set point and high urinary calcium. Clinical presentation may vary from mild asymptomatic to severe hypocalcemia with multiple electrolyte abnormalities. 


Case(s) Description :

We present a case of a 60-year-old female who had multiple hospitalizations and visits to the emergency room with complaints of facial numbness, paresthesia, muscle cramps, and seizures. On exam, she was a well-appearing female with no dysmorphic features or skin changes. Chvostek’s and Trousseau’s signs were positive. Despite being on oral supplemental calcium, her ionized calcium level was 0.63 mmol/L on presentation. Endocrinology was consulted for hypocalcemia refractory to repeated intravenous calcium gluconate doses. Further work-up revealed hypomagnesemia to 1.3 mg/dL, hypokalemia to 2.5 mmol/L, metabolic alkalosis with bicarbonate 31 mmol/L, and an inappropriately low PTH of 21.6 pg/mL given the degree of hypocalcemia. Medical records showed her hypocalcemia to be chronic. As per the patient, her siblings also had a history of hypocalcemia but never presented with similar signs and symptoms. Further testing confirmed a gain-of-function mutation in the CaSR associated with ADH and a classic Bartter syndrome type V phenotype. Genetic analysis revealed a missense mutation in nucleotide c.492+19G >A that resulted in a glycine to aspartic acid change in the CaSR. Given her intractable symptoms, the decision was made to initiate treatment with Teriparatide 20 mcg daily. Within a few days to weeks, her symptoms improved, and serum electrolyte levels stabilized without requiring multiple doses of intravenous repletion.


Discussion :

This case illustrates that the severity of symptoms in ADH is independent of age, mutation type, or mode of inheritance but related to the degree of hypocalcemia and hypomagnesemia. Standard medical therapy with calcium and vitamin D supplementation can often worsen hypercalciuria causing renal manifestations, thus making Teriparatide an effective treatment option. ADH can be insidious in presentation, like in our patient, and the diagnosis can often be missed unless there is a high degree of clinical suspicion.