Familial Hypocalciuric Hypercalcemia 3
Disease Details
Family Health Simplified
- Description
- Familial hypocalciuric hypercalcemia type 3 (FHH3) is a genetic disorder characterized by the body's atypical regulation of calcium, leading to lifelong elevated blood calcium levels with low calcium excretion in urine and generally normal or mildly elevated parathyroid hormone levels.
- Type
- Familial hypocalciuric hypercalcemia type 3 (FHH3) is transmitted in an autosomal dominant manner.
- Signs And Symptoms
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Familial hypocalciuric hypercalcemia type 3 (FHH3) is a rare genetic condition. Signs and symptoms typically include:
1. Mild to moderate hypercalcemia (high calcium levels in the blood).
2. Hypocalciuria (low calcium levels in the urine).
3. Generally asymptomatic or mild symptoms, such as fatigue, weakness, or mild cognitive difficulties.
4. Sometimes can be associated with hypermagnesemia (elevated magnesium levels).
5. Rarely, more significant symptoms like pancreatitis or chondrocalcinosis may occur.
Many individuals with FHH3 may not exhibit any noticeable symptoms and are often diagnosed incidentally through blood tests. - Prognosis
- Familial hypocalciuric hypercalcemia type 3 (FHH3) generally has a benign prognosis. Most individuals with this condition experience mild hypercalcemia and do not exhibit significant symptoms or require treatment. The condition is caused by mutations in the CASR gene, which affects calcium sensing. Complications are rare, but regular monitoring of calcium levels is recommended to manage any potential issues.
- Onset
- Familial Hypocalciuric Hypercalcemia (FHH) type 3 typically features a lifelong, mild elevation of blood calcium levels that often begins in childhood or early adulthood. However, the exact age of onset can vary among individuals.
- Prevalence
- The prevalence of familial hypocalciuric hypercalcemia type 3 (FHH3) is not well-documented, and specific data on its occurrence is generally not available (nan). FHH3 is a rare genetic condition characterized by elevated levels of calcium in the blood with low levels of calcium in the urine.
- Epidemiology
- Familial Hypocalciuric Hypercalcemia type 3 (FHH3) is a very rare genetic disorder, and due to its rarity, comprehensive epidemiological data are not readily available. The condition is inherited in an autosomal dominant manner and is caused by mutations in the AP2S1 gene. The precise prevalence is unknown, but it is less common compared to other types of hypocalciuric hypercalcemia, such as FHH1, which is linked to CASR gene mutations.
- Intractability
- Familial Hypocalciuric Hypercalcemia Type 3 (FHH3) is generally not considered intractable in terms of causing severe health problems. It is a genetic condition characterized by mild to moderate hypercalcemia (high levels of calcium in the blood) with normal or low levels of calcium in the urine. Most individuals with FHH3 lead normal lives without significant symptoms or complications. However, because it is a genetic condition, there is no cure, and the hypercalcemia typically persists lifelong. Treatment is usually not required, but regular monitoring by a healthcare provider is advised.
- Disease Severity
- Familial Hypocalciuric Hypercalcemia type 3 (FHH3) usually presents as a benign condition with mild to moderate hypercalcemia. Most individuals with FHH3 are asymptomatic or experience minimal symptoms. Serious complications are rare, and the condition typically does not affect life expectancy or lead to significant health problems.
- Healthcare Professionals
- Disease Ontology ID - DOID:0060702
- Pathophysiology
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Familial Hypocalciuric Hypercalcemia Type 3 (FHH3) is a genetic disorder affecting calcium homeostasis. It is caused by mutations in the CASR gene that encodes the calcium-sensing receptor (CaSR). This receptor is critical in maintaining calcium levels by regulating parathyroid hormone (PTH) release and calcium reabsorption in the kidneys.
In FHH3, the mutated CaSR has a reduced sensitivity to calcium, leading to decreased inhibition of PTH release despite elevated serum calcium levels. This results in mild to moderate hypercalcemia with relatively low levels of calcium in the urine (hypocalciuria). The condition is typically asymptomatic and benign, often detected incidentally through routine blood tests. - Carrier Status
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The concept of "carrier status" typically applies to recessive genetic conditions, where an individual carries one copy of a mutated gene but does not show disease symptoms. Familial Hypocalciuric Hypercalcemia (FHH) is generally inherited in an autosomal dominant manner, meaning only one copy of the mutated gene can cause the condition. FHH3 specifically involves mutations in the GNA11 gene.
Therefore, the term "carrier status" is not applicable to FHH3. Instead, individuals who inherit the mutated GNA11 gene will likely develop symptoms of the condition. - Mechanism
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Familial hypocalciuric hypercalcemia type 3 (FHH3) is a genetic disorder characterized by elevated levels of serum calcium, low urinary calcium excretion, and normal or mildly elevated parathyroid hormone levels.
### Mechanism:
The primary mechanism of FHH3 involves a defect in calcium sensing by the parathyroid glands and kidneys. This leads to an altered feedback mechanism that results in inappropriate regulation of calcium, leading to hypercalcemia with low calcium excretion in the urine (hypocalciuria).
### Molecular Mechanisms:
FHH3 is caused by mutations in the GNA11 gene, which encodes the G protein subunit alpha-11 (Gα11). Gα11 is a critical component of the calcium-sensing receptor (CaSR) signaling pathway. The CaSR is a G protein-coupled receptor that plays a key role in maintaining calcium homeostasis by regulating parathyroid hormone (PTH) secretion and renal calcium reabsorption.
1. **Mutations in GNA11**: These mutations lead to a loss of function or altered function of the Gα11 protein, which impairs the signal transduction from the CaSR to downstream effectors.
2. **Calcium Sensing**: The impaired Gα11 function results in a reduced sensitivity of the parathyroid glands and kidneys to circulating calcium levels.
3. **Elevated PTH**: Due to reduced sensitivity, the parathyroid glands secrete PTH even when serum calcium levels are elevated, resulting in hypercalcemia.
4. **Hypocalciuria**: The kidneys also fail to appropriately excrete calcium due to the defective CaSR signaling, leading to low calcium levels in the urine.
Overall, FHH3 is characterized by a disrupted calcium homeostasis due to mutations in the GNA11 gene, affecting the signaling pathway of the calcium-sensing receptor. - Treatment
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Familial Hypocalciuric Hypercalcemia type 3 (FHH3) is a genetic disorder characterized by elevated levels of calcium in the blood along with low urinary calcium excretion. Typically, this condition does not require specific treatment as it is generally asymptomatic and considered a benign disorder. However, it is important to distinguish FHH3 from primary hyperparathyroidism, as the latter may require surgical intervention.
Regular monitoring of calcium levels and clinical assessment is usually sufficient. In rare symptomatic cases or if complications arise, treatment should be tailored by a healthcare professional familiar with the patient's overall health and specific genetic condition. - Compassionate Use Treatment
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Familial hypocalciuric hypercalcemia type 3 (FHH3) is a rare genetic disorder that affects calcium regulation. There are no established compassionate use treatments specifically for FHH3, and standard management often involves observation rather than active intervention, given that the condition is generally benign and asymptomatic.
As for off-label or experimental treatments, there are limited data available. However, some avenues of research and potential treatments could include:
1. **Calcimimetics**: These drugs mimic calcium and can activate the calcium-sensing receptor (CaSR). While not specifically approved for FHH3, calcimimetics like cinacalcet are used off-label in conditions with abnormal calcium metabolism, such as primary hyperparathyroidism and could theoretically be considered.
2. **Bisphosphonates**: These drugs inhibit bone resorption. Their use is more traditional in hypercalcemia of malignancy or osteoporosis and there is no substantial evidence supporting their use in FHH3.
3. **Genetic research and gene therapy**: Advances in genetic understanding and manipulation may provide potential future therapies, although these remain largely experimental at this point.
It's important to have ongoing discussions with a healthcare provider specializing in endocrinology or genetics to explore potential individualized treatment options and to monitor the patient’s condition. - Lifestyle Recommendations
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Familial hypocalciuric hypercalcemia type 3 (FHH3) is a genetic condition characterized by elevated levels of calcium in the blood with low calcium levels in the urine. For managing FHH3, there are a few general lifestyle recommendations:
1. **Regular Monitoring**: Regular blood tests to monitor calcium levels and kidney function are essential.
2. **Hydration**: Adequate hydration can help manage calcium levels and reduce the risk of kidney stones.
3. **Dietary Intake**: Consult with a healthcare provider about appropriate calcium and Vitamin D intake. Reducing dietary calcium may be recommended in some cases.
4. **Avoid Certain Medications**: Some medications, like thiazide diuretics, can increase calcium levels and should be used cautiously.
5. **Physical Activity**: Regular exercise can help maintain overall health and bone density.
6. **Consult a Specialist**: Regular follow-ups with an endocrinologist or a geneticist familiar with FHH3 are recommended for personalized management plans.
Always consult with a healthcare provider for tailored advice and before making any significant changes to your lifestyle. - Medication
- For familial hypocalciuric hypercalcemia type 3 (FHH3), there are no specific medications routinely prescribed as treatment is generally not required. The condition is typically benign and managed conservatively. Regular monitoring of calcium levels and routine follow-up with a healthcare provider are recommended. Adjustments are made only if symptomatic hypercalcemia occurs.
- Repurposable Drugs
- Familial hypocalciuric hypercalcemia 3 (FHH3) is a genetic disorder characterized by lifelong mild-to-moderate hypercalcemia, hypocalciuria, and normal or mildly elevated parathyroid hormone levels. As of now, there are no specific repurposable drugs identified for this condition. Treatment is generally not required unless severe symptoms or complications arise. Monitoring and managing calcium levels through diet and lifestyle adjustments are usually recommended.
- Metabolites
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Familial hypocalciuric hypercalcemia type 3 (FHH3) is characterized by elevated levels of serum calcium. The primary metabolites typically impacted in FHH3 include:
1. **Serum Calcium:** Elevated levels.
2. **Parathyroid Hormone (PTH):** Often normal or slightly elevated relative to the hypercalcemia.
3. **Urinary Calcium:** Low to normal excretion despite hypercalcemia (hypocalciuria).
These metabolic disturbances arise due to mutations affecting calcium-sensing pathways, commonly involving the GNA11 gene in FHH3. - Nutraceuticals
- For familial hypocalciuric hypercalcemia type 3 (FHH3), there is currently no specific nutraceutical treatment recommended. Management typically involves monitoring and addressing symptoms rather than supplementing specific nutrients. It's crucial to consult healthcare providers for personalized advice.
- Peptides
- Familial hypocalciuric hypercalcemia 3 (FHH3) is a genetic disorder that affects calcium homeostasis. It is associated with mutations in the AP2S1 gene, which encodes the sigma subunit of the adaptor protein 2 complex. This disorder leads to elevated levels of serum calcium (hypercalcemia) and unusually low levels of calcium in the urine (hypocalciuria). Peptides are not directly associated with FHH3, as it primarily involves genetic mutations affecting calcium-sensing receptors.