Autosomal Dominant Hypocalcemia 1
Disease Details
Family Health Simplified
- Description
- Autosomal dominant hypocalcemia 1 is a genetic disorder characterized by low levels of calcium in the blood due to mutations in the CASR gene, which encodes a calcium-sensing receptor.
- Type
- The type of genetic transmission for autosomal dominant hypocalcemia 1 is autosomal dominant.
- Signs And Symptoms
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Autosomal Dominant Hypocalcemia 1 (ADH1):
**Signs and Symptoms:**
1. **Hypocalcemia:** Low levels of calcium in the blood, which can lead to:
- Muscle cramps or spasms (tetany)
- Seizures
- Numbness and tingling, particularly around the mouth or in the extremities.
2. **Hypercalciuria:** High levels of calcium in the urine, which can lead to:
- Kidney stones
- Potential kidney damage over time.
3. **Neuropsychiatric Symptoms:**
- Irritability
- Depression
- Anxiety
4. **Other Possible Symptoms:**
- Fatigue
- Weakness
- Difficulty concentrating
ADH1 is typically caused by mutations in the CASR gene, which affect calcium regulation in the body. - Prognosis
- Autosomal Dominant Hypocalcemia 1 (ADH1) generally has a favorable prognosis with appropriate management. Patients with ADH1 may need lifelong monitoring and treatment to maintain calcium levels within a normal range. Early diagnosis and regular follow-up with healthcare providers are essential to prevent complications such as seizures, muscle cramps, and cardiac issues. Standard treatments might include calcium and active vitamin D supplements, though care must be taken to avoid hypercalciuria and subsequent kidney complications. Each patient's prognosis can vary based on the specific mutation and the severity of symptoms.
- Onset
- Autosomal Dominant Hypocalcemia 1 (ADH1) typically has its onset in infancy or early childhood. Please specify what "nan" refers to if you need information on a specific aspect.
- Prevalence
- The prevalence of Autosomal Dominant Hypocalcemia 1 (ADH1) is not well-defined but is considered to be a rare genetic disorder.
- Epidemiology
- Autosomal Dominant Hypocalcemia Type 1 (ADH1) is a rare genetic disorder with a low prevalence. Epidemiological data are limited due to its rarity. It occurs due to mutations in the calcium-sensing receptor (CASR) gene. The exact incidence is not well defined, but cases have been reported globally across various populations.
- Intractability
- Autosomal Dominant Hypocalcemia 1 (ADH1) is not necessarily intractable. It is a genetic condition characterized by low levels of calcium in the blood due to mutations in the CaSR gene. While there is no cure for the genetic mutation itself, the symptoms and complications can often be managed with appropriate medical treatment, such as calcium and vitamin D supplements and monitoring by healthcare professionals.
- Disease Severity
- Autosomal Dominant Hypocalcemia Type 1 (ADH1) is generally characterized by mild to moderate disease severity. However, the severity can vary among individuals. Symptoms may include muscle cramps, tetany (muscle spasms), seizures, and other signs of hypocalcemia. In some cases, there may be associated complications such as recurrent kidney stones or nephrocalcinosis due to hypercalciuria (high urinary calcium levels).
- Healthcare Professionals
- Disease Ontology ID - DOID:0090107
- Pathophysiology
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**Pathophysiology of Autosomal Dominant Hypocalcemia 1 (ADH1):**
Autosomal Dominant Hypocalcemia 1 is primarily caused by gain-of-function mutations in the calcium-sensing receptor (CASR) gene, which is located on chromosome 3q21. The CASR is a critical regulator of parathyroid hormone (PTH) secretion and calcium homeostasis. In ADH1, mutations in the CASR gene enhance the sensitivity of the receptor to extracellular calcium levels.
This heightened sensitivity leads to an inappropriate suppression of PTH secretion even when blood calcium levels are low. Without sufficient PTH, the body cannot adequately increase calcium reabsorption from the kidneys, release calcium from bones, or absorb calcium from the digestive tract, leading to hypocalcemia (low blood calcium levels). Additionally, low PTH levels can cause hyperphosphatemia (high blood phosphate levels), as PTH normally promotes phosphate excretion in the kidneys.
Overall, the excessive activity of the mutated CASR leads to a consistent state of low blood calcium, which is characteristic of ADH1. This can lead to various clinical manifestations, including muscle cramps, tetany, seizures, and other symptoms associated with hypocalcemia. - Carrier Status
- For autosomal dominant hypocalcemia 1, the concept of "carrier status" does not apply. Since it is an autosomal dominant disorder, possessing just one copy of the mutated gene is sufficient to cause the condition. Therefore, you cannot be a carrier without expressing some degree of symptoms.
- Mechanism
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Autosomal dominant hypocalcemia 1 (ADH1) is primarily caused by gain-of-function mutations in the calcium-sensing receptor (CASR) gene. This receptor plays a key role in regulating calcium homeostasis by modulating parathyroid hormone (PTH) secretion and renal calcium reabsorption.
**Mechanism:**
In ADH1, the mutant CASR is overly sensitive to extracellular calcium levels. This heightened sensitivity leads the receptor to signal as if calcium levels are high, even when they are not, resulting in inappropriate suppression of PTH secretion. Reduced PTH levels lead to decreased renal calcium reabsorption and increased renal calcium excretion, ultimately causing hypocalcemia (low blood calcium levels).
**Molecular Mechanisms:**
- **CASR Activation:** The mutated CASR is constitutively active or has an increased response to normal or even low extracellular calcium, which results in continuous signaling for the suppression of PTH release.
- **PTH Suppression:** The suppression of PTH leads to decreased bone resorption of calcium and reduced activation of vitamin D in the kidneys, both contributing to lower calcium absorption from the gastrointestinal tract and reabsorption from the kidneys.
- **Renal Calcium Handling:** The inappropriate activation of CASR in the kidneys leads to increased calcium excretion, worsening hypocalcemia.
Overall, the molecular mechanism involves dysregulated calcium signaling due to an overactive CASR, which disrupts the balance of calcium homeostasis by limiting the body’s ability to raise calcium levels appropriately in response to physiological needs. - Treatment
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Treatment for autosomal dominant hypocalcemia 1 (ADH1) primarily focuses on managing hypocalcemia and preventing symptoms related to low calcium levels. Common treatments include:
1. **Calcium Supplements:** To directly increase calcium levels in the blood.
2. **Activated Vitamin D (e.g., Calcitriol or Alfacalcidol):** To enhance intestinal absorption of calcium and maintain appropriate blood calcium levels.
3. **Thiazide Diuretics:** These may be used in some cases to reduce urinary calcium excretion and help maintain calcium levels.
Regular monitoring of blood calcium, magnesium, and phosphate levels is necessary to adjust treatment and avoid complications. Consultation with an endocrinologist is often recommended for long-term management. - Compassionate Use Treatment
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Autosomal Dominant Hypocalcemia 1 (ADH1) is a condition characterized by low calcium levels due to mutations in the calcium-sensing receptor (CaSR) gene. Treatment typically focuses on managing hypocalcemia.
### Compassionate Use Treatment:
1. **Recombinant Parathyroid Hormone (PTH):**
- In some cases, synthetic PTH may be considered under compassionate use to help manage calcium levels.
### Off-Label or Experimental Treatments:
1. **Calcilytics:**
- Drugs designed to inhibit the CaSR, potentially increasing calcium levels. These are experimental and not yet widely available.
2. **Calcitriol:**
- The active form of vitamin D, used off-label to enhance calcium absorption from the gut.
3. **Thiazide Diuretics:**
- These medications might be used to reduce urinary calcium excretion, thus indirectly helping to maintain serum calcium levels.
Close medical supervision is essential when using these treatments due to potential risks and the need for regular monitoring of calcium and other electrolytes. - Lifestyle Recommendations
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For individuals with Autosomal Dominant Hypocalcemia 1 (ADH1), lifestyle recommendations primarily focus on managing calcium levels and maintaining overall health. Here are some suggestions:
1. **Regular Monitoring**: Regular check-ups and blood tests to monitor calcium and parathyroid hormone levels are essential.
2. **Diet**: Maintain a balanced diet rich in calcium and vitamin D to help manage calcium levels. Low-fat dairy products, leafy green vegetables, and fortified foods can be beneficial.
3. **Hydration**: Staying well-hydrated is crucial, as dehydration can exacerbate symptoms.
4. **Avoid Excessive Calcium**: Avoid excessive calcium intake through supplements without medical advice, as it may lead to complications.
5. **Exercise**: Engage in regular physical activities to promote bone health, but avoid overly strenuous exercises that may cause muscle cramps or weakness.
6. **Medication Adherence**: Follow prescribed medications and therapies exactly as directed by a healthcare provider.
7. **Avoid Triggers**: Identify and avoid triggers that may exacerbate symptoms, such as certain foods, stress, or intense physical activity.
8. **Educate and Plan**: Educate yourself about the condition and have an emergency plan in place for managing acute hypocalcemia symptoms.
Consulting with a healthcare provider for personalized advice is always recommended. - Medication
- For autosomal dominant hypocalcemia 1 (ADH1), treatment often involves managing hypocalcemia with calcium and active vitamin D supplements, such as calcitriol. Additionally, magnesium supplementation may be necessary if hypomagnesemia is present. It's crucial to monitor and adjust the medication carefully to avoid complications such as hypercalciuria and nephrocalcinosis. In severe cases, recombinant human parathyroid hormone (rhPTH) may be considered. Consultation with a healthcare provider specialized in endocrine disorders is recommended for personalized management.
- Repurposable Drugs
- For autosomal dominant hypocalcemia type 1, repurposable drugs are not typically well-documented due to the rarity of this condition. Treatment usually focuses on managing symptoms and maintaining balanced blood calcium levels. Traditional approaches include calcium supplements and active forms of vitamin D, such as calcitriol. Emerging research or case studies may identify new potential therapeutic uses for existing drugs over time, but specific repurposable drugs for this condition are currently not well-established.
- Metabolites
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Autosomal Dominant Hypocalcemia 1 (ADH1) is a disorder characterized by low levels of calcium in the blood. Metabolites involved in ADH1 can include:
1. **Calcium**: Low levels of calcium in the blood (hypocalcemia).
2. **Phosphate**: May be normal or elevated due to the impact on calcium-phosphate homeostasis.
3. **Parathyroid Hormone (PTH)**: Typically low or inappropriately normal, given the low calcium levels, due to the mutation in the calcium-sensing receptor (CaSR) gene.
This summary includes some of the key metabolites associated with ADH1. - Nutraceuticals
- Autosomal Dominant Hypocalcemia 1 (ADH1) is a disorder caused by mutations in the CASR gene, affecting calcium regulation. Nutraceuticals for managing ADH1 focus primarily on augmenting calcium levels and include calcium supplements and active forms of vitamin D (like calcitriol) to enhance calcium absorption and maintain bone health. There is no specific role of nanotechnology (nan) mentioned in the current standard treatment protocols for ADH1.
- Peptides
- Autosomal dominant hypocalcemia 1 (ADH1) is a genetic disorder that affects calcium homeostasis. It is caused by mutations in the CASR (calcium-sensing receptor) gene located on chromosome 3. While peptides themselves might not directly cause this condition, the mutation in the receptor—a protein that could be considered in a broad sense as involving peptide chains—alters the way the body regulates calcium levels. There is no direct association between ADH1 and nanoparticles (nan). Treatment typically focuses on managing calcium levels in the body.