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Autosomal Dominant Hypocalcemia


Autosomal dominant hypoparathyroidism is a clinical disorder characterized by hypocalcemia and hyperphosphatemia, due to insufficient parathyroid hormone (PTH) levels to maintain normal extracellular fluid calcium concentration.

Clinical Manifestations

Acute hypocalcemia causes neuromuscular irritability, including perioral paresthesias, tingling of the fingers and toes, and spontaneous or latent tetany with grand mal seizures and even laryngeal spasm. Chronically, hypocalcemia can be asymptomatic and only become apparent after routine blood screening. Alternatively, it can manifest with mild neuromuscular irritability, calcification of the basal ganglia, extrapyramidal disorders, cataracts, alopecia, abnormal dentition, coarse brittle hair, mental retardation, or personality disorders.


Hypocalcemia and hyperphosphatemia are found in the presence of normal renal function. Serum PTH levels are low or undetectable. Renal calcium excretion is elevated.


Autosomal dominant hypoparathyroidism is caused by activating mutations of the CASR gene. Since the receptor negatively regulates calcium tubular resorption, receptor activation leads to hypercalciuria even in the presence of hypocalcemia; and because the receptor participates in a negative feedback loop regulating parathyroid function, CASR activation is accompanied by hypoparathyroidism. Occasionally activating CASR mutations can produce sporadic hypoparathyroidism as well. For the genetic study it will be necessary samples of the index case and the parents.


Thiazides can be useful in reducing calciuria, and can maintain normal serum calcium levels associated with 1,25-dihydroxyvitamin D3 or 1-alpha-hydroxyvitamin D3.



Treatment with vitamin D or its metabolites may induce hypercalciuria, nephrocalcinosis, and renal impairment.


  1. Baron, J., Winer, K. K., Yanovski, J. A., Cunningham, A. W., Laue, L., Zimmerman, D., Cutler, G. B., Jr.Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism.Hum. Molec. Genet. 5: 601-606, 1996.