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Familial Hypocalciuric Hypercalcemia 2

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Description: Familial hypocalciuric hypercalcemia 2 is a genetic disorder characterized by elevated blood calcium levels, low urinary calcium excretion, and generally mild or asymptomatic presentations.
Type: Familial hypocalciuric hypercalcemia type 2 (FHH2) is primarily transmitted in an autosomal dominant manner.
Signs And Symptoms: Familial hypocalciuric hypercalcemia type 2 (FHH2) is a genetic disorder characterized by:

- Mild to moderate hypercalcemia (elevated calcium levels in the blood).
- Hypocalciuria (low calcium levels in urine).
- Normal or mildly elevated parathyroid hormone (PTH) levels.

Many individuals remain asymptomatic, while others may experience symptoms such as fatigue, weakness, or mild cognitive disturbances. Due to its often mild presentation, FHH2 is frequently discovered incidentally during routine blood tests.
Prognosis: Familial hypocalciuric hypercalcemia type 2 (FHH2) generally has a benign prognosis. It is a genetic condition characterized by elevated serum calcium levels and low urinary calcium excretion. Most individuals with FHH2 remain asymptomatic and do not require treatment. The condition is typically managed through monitoring rather than intervention.
Onset: The onset of Familial Hypocalciuric Hypercalcemia type 2 (FHH2) typically occurs in childhood or adolescence. The condition is usually asymptomatic and often discovered incidentally through routine blood tests showing elevated levels of calcium.
Prevalence: Familial hypocalciuric hypercalcemia type 2 (FHH2) is an extremely rare genetic disorder, and specific prevalence data is not well-documented. Overall, familial hypocalciuric hypercalcemia (FHH), encompassing all types, is estimated to occur in about 1 in 78,000 individuals.
Epidemiology: Familial hypocalciuric hypercalcemia 2 (FHH2) is an extremely rare genetic disorder. Prevalence data specific to FHH2 is limited due to its rarity and the challenges in distinguishing it from other types of hypercalcemia, particularly familial hypocalciuric hypercalcemia types 1 and 3. Epidemiological studies typically focus on the more common forms, and precise prevalence rates for FHH2 are not well-documented.
Intractability: Familial hypocalciuric hypercalcemia type 2 (FHH2) is generally not considered intractable. It is a genetic condition typically characterized by lifelong, mild to moderate hypercalcemia that is usually asymptomatic or causes mild symptoms. Treatment is usually not required, and the condition does not lead to severe clinical complications in most cases. Regular monitoring and management of calcium levels may be advised, but the disease itself is typically manageable.
Disease Severity: Disease severity for Familial Hypocalciuric Hypercalcemia 2 (FHH2) is generally mild. Most individuals are asymptomatic and do not require treatment. However, monitoring is recommended as complications are possible but rare.
Healthcare Professionals: Disease Ontology ID - DOID:0060701
Pathophysiology: Familial hypocalciuric hypercalcemia 2 (FHH2) is a genetic disorder characterized by mild to moderate hypercalcemia, low urinary calcium excretion, and normal to mildly elevated parathyroid hormone (PTH) levels. The pathophysiology of FHH2 involves mutations in the GNA11 gene, which encodes the G11α subunit of a G-protein. This subunit plays a critical role in the calcium-sensing receptor (CaSR) signaling pathway that regulates calcium homeostasis. Mutations in GNA11 lead to decreased sensitivity of CaSR to extracellular calcium levels, resulting in inappropriate parathyroid hormone release and reduced renal calcium excretion, ultimately causing the persistent hypercalcemia and hypocalciuria seen in FHH2.
Carrier Status: Carrier status for familial hypocalciuric hypercalcemia type 2 (FHH2) generally refers to individuals who have one mutated copy of the gene associated with the disorder. In this case, FHH2 is typically associated with mutations in the GNA11 gene. Carriers may not experience severe symptoms but can still have mild biochemical abnormalities, such as slightly elevated calcium levels.
Mechanism: Familial Hypocalciuric Hypercalcemia Type 2 (FHH2) is a genetic disorder characterized by elevated levels of serum calcium, low urinary calcium excretion, and normal or mildly elevated parathyroid hormone (PTH) levels.

**Mechanism:**
FHH2 results from mutations in the GNA11 gene, which encodes the G-protein subunit alpha-11 (Gα11). This protein is involved in the calcium-sensing receptor (CaSR) signaling pathway. The CaSR is crucial for maintaining calcium homeostasis by regulating parathyroid hormone secretion and renal calcium reabsorption.

**Molecular Mechanisms:**
- **Mutation in GNA11:** Mutations in GNA11 disrupt the normal function of the Gα11 protein, impairing the CaSR signaling pathway.
- **Impaired Calcium Sensing:** The altered signaling reduces the sensitivity of the parathyroid gland and kidneys to extracellular calcium levels. Consequently, higher calcium concentrations are necessary to suppress PTH secretion and decrease renal calcium reabsorption.
- **Serum Calcium Regulation:** This results in elevated serum calcium levels (hypercalcemia) and reduced calcium excretion in urine (hypocalciuria), despite normal or mildly elevated PTH levels.

Understanding these mechanisms helps in distinguishing FHH2 from other hypercalcemic disorders, particularly primary hyperparathyroidism.
Treatment: Familial hypocalciuric hypercalcemia type 2 (FHH2) typically requires no treatment because it is usually a benign condition. However, it is important to distinguish it from primary hyperparathyroidism, which may require surgical intervention. Regular monitoring of calcium levels and avoiding unnecessary treatments are generally recommended. Family members might also benefit from genetic counseling and monitoring.
Compassionate Use Treatment: Familial Hypocalciuric Hypercalcemia Type 2 (FHH2) is a rare genetic disorder characterized by mild to moderate hypercalcemia, normal or elevated parathyroid hormone levels, and low urinary calcium excretion. Treatment is generally not required because the condition is usually benign and asymptomatic.

In cases where intervention might be considered due to symptomatic hypercalcemia (which is rare), possible approaches could include:

1. **Calcimimetics**: These drugs, such as cinacalcet, can be used off-label to lower calcium levels by increasing the sensitivity of the calcium-sensing receptors on the parathyroid glands, thereby reducing parathyroid hormone secretion.

2. **Bisphosphonates**: Although their use is more common in hypercalcemia of malignancy and osteoporosis, bisphosphonates might be considered to reduce bone resorption and thereby lower calcium levels, although this would be an off-label use.

3. **Investigational treatments**: Depending on ongoing research and clinical trials, new treatments might be under investigation, but specific therapies directly targeting FHH2 are not standard at this time.

Generally, ongoing monitoring and avoidance of unnecessary interventions are recommended due to the typically mild nature of the condition. For detailed experimental treatment options, participation in clinical trials may be explored.
Lifestyle Recommendations: For familial hypocalciuric hypercalcemia type 2 (FHH2), lifestyle recommendations primarily focus on managing symptoms and maintaining overall health. Here are some general guidelines:

1. **Regular Monitoring**: Regular check-ups with a healthcare provider to monitor calcium levels, kidney function, and overall health are essential.

2. **Hydration**: Ensure adequate hydration to help maintain kidney function and reduce the risk of kidney stones, which can be a concern in hypercalcemia.

3. **Dietary Considerations**: While there are no specific dietary restrictions universally recommended, individuals should avoid excessive calcium and vitamin D intake without professional guidance.

4. **Exercise**: Maintain a regular exercise routine to support overall health, with attention to bone strength and cardiovascular health.

5. **Medication Management**: Adhere to any prescribed medications or supplements, and consult your healthcare provider before starting new ones.

6. **Avoid Certain Medications**: Some medications, such as thiazide diuretics, can increase calcium levels. Discuss any current medications with a healthcare provider to avoid exacerbating hypercalcemia.

7. **Family Planning**: Since FHH2 is inherited, genetic counseling may be beneficial for affected individuals considering starting a family.

Consult with a healthcare provider for personalized recommendations that consider individual health status and needs.
Medication: Familial hypocalciuric hypercalcemia 2 (FHH2) is a genetic condition characterized by elevated levels of calcium in the blood (hypercalcemia) and low levels of calcium in the urine (hypocalciuria). There are generally no specific medications required for FHH2, as it is a benign condition and typically does not cause significant symptoms or health problems. Management usually involves monitoring calcium levels and regular follow-ups with a healthcare provider. If symptomatic, treatment is tailored to individual symptoms and needs.
Repurposable Drugs: Currently, there are no well-established repurposable drugs specifically for treating Familial Hypocalciuric Hypercalcemia type 2 (FHH2). Management primarily involves monitoring calcium levels and being cautious about unnecessary interventions, such as avoiding parathyroidectomy, which can be ineffective. If you have specific concerns, consulting a healthcare provider or specialist is recommended for personalized advice.
Metabolites: For familial hypocalciuric hypercalcemia type 2 (FHH2), key metabolites involved include elevated levels of calcium and parathyroid hormone (PTH) in the blood. Urinary calcium excretion is typically low or inappropriately normal, distinguishing it from primary hyperparathyroidism.
Nutraceuticals: For familial hypocalciuric hypercalcemia type 2 (FHH2), there are no specific nutraceuticals that are proven treatments or have substantial evidence to modify the disease. Management generally revolves around monitoring and avoiding unnecessary interventions, as the condition is typically benign. Always consult with a healthcare professional for personalized advice and management plans.
Peptides: Familial Hypocalciuric Hypercalcemia type 2 (FHH2) is a genetic disorder characterized by elevated blood calcium levels, low urinary calcium excretion, and normal or slightly elevated parathyroid hormone (PTH) levels. It is associated with mutations in the GNA11 gene. Peptides are not specifically noted in the context of FHH2, as the condition primarily involves genetic mutations affecting calcium-sensing pathways rather than peptide dysfunction.