Autosomal dominant hypocalcemia
Autosomal dominant hypocalcemia is a genetic condition characterized by low blood calcium levels, often resulting in muscle irritability, cramping, or seizures, though many affected individuals remain asymptomatic.
Overview
Autosomal dominant hypocalcemia is characterized by low levels of calcium in the blood (hypocalcemia). Affected individuals may also experience an imbalance of other molecules, including high levels of phosphate (hyperphosphatemia) or low levels of magnesium (hypomagnesemia). Some individuals also have low levels of parathyroid hormone (hypoparathyroidism), which is responsible for regulating blood calcium. While these imbalances can cause various symptoms, approximately half of those affected have no associated health problems.
Symptoms
The most common features include:
- Muscle spasms in the hands and feet (carpopedal spasms)
- Muscle cramping
- Prickling or tingling sensations (paresthesias)
- Twitching of the nerves and muscles (neuromuscular irritability)
More severely affected individuals may develop seizures, typically in infancy or childhood. In some cases, symptoms only manifest during episodes of illness or fever. Additionally, some individuals develop high levels of calcium in their urine (hypercalciuria), which can lead to calcium deposits in the kidneys (nephrocalcinosis) or kidney stones (nephrolithiasis). Abnormal calcium deposits may also form in the brain, typically in the basal ganglia.
A small percentage of individuals may exhibit features of Bartter syndrome, including low potassium (hypokalemia), low magnesium, high levels of the hormone aldosterone (hyperaldosteronism), and an elevated blood pH (metabolic alkalosis).
Causes
The condition is distinguished by two genetic types:
- Type 1: Caused by mutations in the CASR gene.
- Type 2: Caused by mutations in the GNA11 gene.
The CASR gene provides instructions for the calcium-sensing receptor (CaSR), which monitors blood calcium levels. The GNA11 gene produces Gα11, a signaling protein that works with CaSR. Mutations in these genes lead to protein overactivity, causing the body to perceive calcium levels as higher than they are and preventing the normal processes that would increase calcium in the blood. This results in persistent hypocalcemia.
Inheritance
This condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene in each cell is sufficient to cause the disorder. While most cases are inherited, some result from new (de novo) mutations in the gene in people with no family history of the disorder.