Bartter syndrome with hypocalcemia

Bartter syndrome with hypocalcemia, also known as Bartter syndrome type 5 or autosomal dominant hypocalcemia with Bartter syndrome, is a rare genetic disorder caused by gain-of-function mutations in the CASR gene encoding the calcium-sensing receptor. This condition combines features of classic Bartter syndrome — a renal tubular disorder — with abnormally low blood calcium levels (hypocalcemia). The overactive calcium-sensing receptor in the kidneys leads to excessive urinary loss of sodium, potassium, chloride, calcium, and magnesium, mimicking the electrolyte disturbances seen in other forms of Bartter syndrome. Key clinical features include hypokalemic metabolic alkalosis, renal salt wasting, hypocalcemia, and hypomagnesemia. Patients may experience muscle cramps, tetany, seizures, weakness, fatigue, polyuria, and polydipsia. The condition primarily affects the kidneys and parathyroid glands. The gain-of-function CASR mutations suppress parathyroid hormone (PTH) secretion, contributing to hypocalcemia, while simultaneously impairing renal tubular reabsorption of electrolytes. This distinguishes it from other Bartter syndrome subtypes, which are caused by defects in ion channels or transporters in the thick ascending limb of the loop of Henle. Onset is typically in infancy or early childhood, though presentation can be variable. Treatment is challenging and focuses on electrolyte replacement, including potassium, magnesium, and cautious calcium supplementation. Nonsteroidal anti-inflammatory drugs (such as indomethacin) may be used to reduce prostaglandin-mediated renal salt wasting. Careful monitoring is essential because excessive calcium supplementation can worsen renal calcium excretion and increase the risk of nephrocalcinosis and kidney stones.

Common questions about Bartter syndrome with hypocalcemia