Autosomal Dominant Hypocalcemia Type 1

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Synonyms

Autosomal dominant hypoparathyroidism, Familial hypocalcemia, HYPOC1, Autosomal dominant hypocalcemia, Familial hypercalciuric hypocalcemia, ADH1,

Overview

Autosomal Dominant Hypocalcemia Type 1 (ADH1) is a rare genetic disorder causing low blood calcium (hypocalcemia) with high calcium in the urine (hypercalciuria) due to a gain-of-function mutation in the CASR gene. This mutation makes the calcium-sensing receptor protein overactive, leading to a decreased parathyroid hormone (PTH) secretion and reduced calcium reabsorption in the kidneys. Symptoms vary, from being asymptomatic to experiencing muscle spasms, tingling sensations, or seizures. 

Symptoms

Symptoms of Autosomal Dominant Hypocalcemia Type 1 (ADH1) include muscle spasms and cramps, tingling or prickling sensations (paresthesias), and seizures, which can sometimes be severe. More than half of affected individuals show no related health problems, but some can experience high levels of calcium in the urine (hypercalciuria), leading to kidney stones (nephrolithiasis) and calcium deposits in the kidneys (nephrocalcinosis). Some individuals may also develop calcium deposits in the brain. 

Causes

Autosomal dominant hypocalcemia type 1 (ADH1) is primarily caused by gain-of-function mutations in the CASR gene, which encodes the calcium-sensing receptor protein. These mutations make the receptor more sensitive to calcium, leading it to suppress parathyroid hormone (PTH) secretion at normal blood calcium levels, resulting in hypocalcemia (low blood calcium). The condition can be inherited from a parent or result from a new mutation in a person with no family history. 

Prevention

There is no cure or way to prevent Autosomal Dominant Hypocalcemia Type 1 (ADH1), which is a genetic condition, but prevention of complications is possible through careful management. Key prevention strategies involve continuous monitoring of calcium levels, preventing maternal and fetal complications during pregnancy with close monitoring and treatment, and using therapies like thiazide diuretics and calcilytics to manage symptoms and reduce the risk of kidney damage. 

Diagnosis

The diagnosis of Autosomal Dominant Hypocalcemia Type 1 (ADH1) involves biochemical testing, such as blood tests for calcium and parathyroid hormone (PTH), and 24-hour urine calcium measurements to check for high urinary calcium levels. A definitive diagnosis requires genetic testing to identify gain-of-function mutations in the CASR gene. A family history of similar symptoms can also help establish a diagnosis. 

Prognosis

The prognosis for Autosomal Dominant Hypocalcemia Type 1 (ADH1) is

variable, ranging from mild to severe, and depends on the effectiveness of management. With appropriate treatment to maintain normal calcium levels, patients can have a normal life expectancy, similar to those with mild forms of other parathyroid disorders. However, complications like seizures, congestive heart failure, nephrocalcinosis (kidney calcification), or basal ganglia calcifications can arise if left untreated or poorly managed. 

Treatment

Treatment for Autosomal Dominant Hypocalcemia Type 1 (ADH1) focuses on

managing symptoms with conventional therapy like calcium supplements and active vitamin D, but also includes emerging treatments such as PTH analogues and calcilytics. The goal is to alleviate symptoms rather than strictly normalizing calcium levels, due to risks like kidney stones and calcifications with traditional therapies. Thiazide diuretics may be considered to reduce urinary calcium excretion.