It is an inherited endocrine disorder characterized by2:
A child has a 50% chance of inheriting the variant associated with ADH1 if one parent is affected.2
Variants in the calcium-sensing receptor (CaSR) are responsible for1,2:
The mechanism of disease in ADH1 is distinct from that of other forms of hypoparathyroidism because of the critical role of the CaSR in both the parathyroid glands and kidneys.2,3
A common sign of ADH1 is low serum calcium, which results in symptoms including tetany, muscle cramps, and spasms. In more severe cases, seizures, laryngospasms, and cardiac arrhythmias are experienced. Conventional treatment (calcium and active vitamin D supplementation) can lead to kidney calcification, kidney stones, and even kidney failure.
*Result of prolonged conventional treatment with calcium supplements and active vitamin D analogues.
People living with hypoparathyroidism, including ADH1, may experience these quality-of-life challenges:
Some people with ADH1 never learn of the underlying genetic cause of their condition and may never receive optimal disease management.
While symptoms may start in infancy, many people with ADH1 may not receive an accurate diagnosis until they are adults.
Patients may receive an incomplete diagnosis, including:
Patients may receive a misdiagnosis based on symptoms:
Genetic testing is recommended for patients with idiopathic hypoparathyroidism.
These CASR variants cause the CaSR to be overly sensitive to calcium, thereby causing it to detect low blood calcium concentration as "normal." This leads to decreased PTH secretion from the parathyroid glands and decreased calcium reabsorption in the kidney—the result is:
Due to the critical role of CaSR on the functions of the parathyroid gland and kidneys, patients with ADH1 often present with both hypocalcemia and hypercalciuria and may experience hypercalciuria-associated complications2,4:
For people living with ADH1, the main goal with conventional therapy is to keep blood calcium concentrations close to, or slightly below, the lower limit of normal to avoid2,3,5:
Serum calcium
(albumin-adjusted or ionized)
Magnesium
Phosphorus
25-hydroxyvitamin D
Serum creatinine (for eGFR)
24-hour urine creatinine
24-hour urine calcium
eGFR=estimated glomerular filtration rate.
Patients with ADH1 should be monitored regularly to assess their blood biochemistry and the risk of hypercalciuria and potential kidney damage.2,6
Currently, there are no medications specifically indicated to treat ADH1. There remains a substantial unmet need for therapies that address the underlying molecular mechanism of ADH1.2,5
References: 1. Mannstadt M, Cianferotti L, Gafni RI, et al. Hypoparathyroidism: genetics and diagnosis. J Bone Miner Res. 2022;37(12):2615-2629. 2. Roszko KL, Stapleton Smith LM, Sridhar AV, et al. Autosomal dominant hypocalcemia type 1: a systematic review. J Bone Miner Res. 2022;37(10):1926-1935. 3. Roszko KL, Bi RD, Mannstadt M. Autosomal dominant hypocalcemia (hypoparathyroidism) types 1 and 2. Front Physiol. 2016;7:458. 4. Pearce SH, Williamson C, Kifor O, et al. A familial syndrome of hypocalcemia with hypercalciuria due to mutations in the calcium-sensing receptor. N Engl J Med. 1996;335(15):1115-1122. 5. Khan AA, Ali DS, Bilezikian JP, et al. Best practice recommendations for the diagnosis and management of hypoparathyroidism. Metabolism. 2025;171:156335. 6. Bollerslev J, Rejnmark L, Marcocci C, et al. European Society of Endocrinology clinical guideline: treatment of chronic hypoparathyroidism in adults. Eur J Endocrinol. 2015;173(2):G1-20. 7. Bollerslev J, Buch O, Cardoso LM, et al. Revised European Society of Endocrinology clinical practice guideline: treatment of chronic hypoparathyroidism in adults. Eur J Endocrinol. 2025;193(5):G49-G78.