autosomal dominant hypocalcemia 1

Autosomal dominant hypocalcemia 1 is a mineral-balance disorder that primarily affects how the body regulates calcium and related electrolytes. It is caused by changes in the CASR gene, which encodes the calcium-sensing receptor that tells the parathyroid glands and kidneys when calcium levels are adequate. Because the condition follows an autosomal dominant inheritance pattern, one altered copy of the gene is enough to cause disease, and affected individuals are seen in multiple generations. Symptoms can start in infancy or childhood, although some people are first recognized in adulthood after an unexpected low-calcium blood test. Precise prevalence figures are not well established, but the condition is considered uncommon in the general population.

Autosomal dominant hypocalcemia 1 typically begins with low calcium levels that trigger muscle cramps, tetany, or tingling around the mouth and fingertips. Infants may have laryngospasm that causes a high pitched cry or brief breathing problems. Seizures, painful numbness, or twitching can appear when calcium falls further. During these episodes children and adults may seem irritable, anxious, or have trouble focusing, but their overall intellectual development is usually normal once calcium is stabilized. Ongoing loss of calcium in the urine can lead to kidney stones, nephrocalcinosis, and over many years a slow drop in kidney function. Blood tests often show low magnesium, high phosphate, and very low parathyroid hormone despite the hypocalcemia. Rare findings include basal ganglia calcification, short stature, or mild electrolyte shifts such as low potassium.

Autosomal dominant hypocalcemia 1 results from pathogenic variants in the CASR gene. The calcium-sensing receptor is expressed in the parathyroid glands, kidneys, and other tissues, where it monitors circulating calcium and helps maintain a narrow physiologic range. Gain-of-function variants make the receptor think calcium levels are higher than they truly are, which suppresses parathyroid hormone release and increases renal calcium loss. The condition is inherited in an autosomal dominant fashion, meaning a parent with the variant has a 50 percent chance of passing it to each child. Even within the same family, the specific symptoms and their intensity can differ markedly, a phenomenon known as variable expressivity. Genetic counseling is recommended for affected individuals and relatives to discuss testing, family planning, and early detection strategies.

Currently, management focuses on supportive care and symptom control. Oral calcium supplementation, active vitamin D analogs, or magnesium replacement may be used to raise serum calcium and reduce neuromuscular irritability, but must be balanced carefully to avoid worsening urinary calcium loss. Thiazide-type diuretics are sometimes considered to lower urinary calcium excretion, again requiring close monitoring. Long-term care typically involves a multidisciplinary team that may include endocrinology, nephrology, and neurology specialists. Regular surveillance is an essential part of care, with periodic measurement of serum and urinary electrolytes, assessment of kidney function, and imaging for nephrocalcinosis or stones so that complications are detected early. Individuals should discuss treatment options and monitoring intervals with their healthcare team to tailor therapy to their specific needs.

With attentive monitoring and individualized management, many people maintain good overall health, although some continue to experience muscle symptoms or develop kidney complications that require additional intervention. Neurological issues such as seizures often respond to correction of calcium levels but may necessitate separate treatment if they persist. Outcomes described in medical literature continue to evolve as standards of care improve, and early recognition allows clinicians to prevent or mitigate long-term kidney damage. Severity and symptoms vary widely between individuals, so predicting the course for any one person is difficult. Families often find it helpful to connect with specialists familiar with calcium and kidney disorders and to seek genetic counseling when planning for the future.

Several clinical trials are currently investigating new treatment approaches that may more precisely target the underlying receptor dysfunction. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.