familial hypocalciuric hypercalcemia 3

Familial hypocalciuric hypercalcemia (FHH) causes hypercalcemia by three genetic mechanisms:

• Inactivating mutations in the calcium-sensing receptor [3]
• The G protein-coupled receptor kinase 3 (GRK3) gene [3]
• The parathyroid hormone-related protein (PTHrP) gene [3]

These genetic mechanisms lead to an overproduction of parathyroid hormone, which in turn causes an increase in blood calcium levels. This condition is characterized by:

• Hypercalcemia: elevated serum calcium level typically above 10.2 mg/dL
• Hypocalciuria: low to moderate levels of calcium in urine
• Normal renal function

FHH is a rare, usually asymptomatic, inherited condition that affects the calcium sensing receptor and its associated pathways [8]. It can be caused by variants in the CASR gene, leading to lifelong elevated calcium levels [7].

References: [3] - 3. by JY Lee · 2018 · Cited by 122 [7] - 7. Familial hypocalciuric hypercalcaemia is a genetic condition caused by variants in the CASR gene that results in lifelong elevated calcium levels. [8] - 8. by L Baraf · 2022 — Familial hypocalciuric hypercalcemia (FHH) is a rare, usually asymptomatic, inherited condition, affecting the calcium sensing receptor and its associated ...

Common Signs and Symptoms of Familial Hypocalciuric Hypercalcemia (FHH) Type 3

People with FHH type 3 may experience a range of symptoms, including:

• High magnesium levels: In addition to high calcium levels, some individuals with FHH type 3 may have elevated magnesium levels in their blood.
• General symptoms of hypercalcemia: These can include:
  • Extreme thirst [4]
  • Frequent urination [4]
  • Pain in the stomach area [3]

It's essential to note that not everyone with FHH will experience these symptoms, and some may remain asymptomatic throughout their lives. If you're concerned about your calcium levels or are experiencing any of these symptoms, consult a healthcare professional for proper evaluation and guidance.

References: [3] - Mar 8, 2024 [4] - Nov 1, 2021

Familial Hypocalciuric Hypercalcemia (FHH) type 3 can be diagnosed through a combination of clinical evaluation and genetic testing.

Clinical Evaluation

• Mild hypophosphatemia is often present in FHH type 3, as mentioned in [3].
• Elevated plasma Parathyroid Hormone (PTH) concentrations are also characteristic of this condition.
• Primary hyperparathyroidism can be clinically similar to FHH, but it can be differentiated by measuring the calcium/creatinine clearance ratio of a 24-hour urine sample, as stated in [7].

Genetic Testing

• The CASR gene is associated with FHH type 3, and next-generation sequencing can detect single nucleotide, deletion-insertion, and copy number variants in this gene, as described in [4].
• Identification of pathogenic variants in the genes responsible for FHH can confirm the diagnosis based on clinical/biochemical presentation, which can assist in differential diagnosis, as stated in [5].

Diagnostic Tests

• A 24-hour urine sample can be used to calculate the calcium/creatinine clearance ratio, which is often low in individuals with FHH type 3.
• Genetic testing for the CASR gene can confirm the diagnosis of FHH type 3.

It's worth noting that FHH type 3 does not usually require treatment, as it is a benign condition. However, genetic testing can provide a definitive diagnosis and help rule out other conditions with similar symptoms.

Familial hypocalciuric hypercalcemia (FHH) type 3 is a rare genetic disorder characterized by elevated calcium levels in the blood, despite low or normal urine calcium excretion. While there is no effective therapy for FHH type 3, research has explored various treatment options to manage symptoms and reduce calcium levels.

Current Treatment Options:

• Cinacalcet: A calcimimetic drug that has been used to treat hypercalcemia in certain symptomatic causes of FHH. It works by activating the calcium-sensing receptor (CaR) on parathyroid gland cells, leading to a decrease in parathyroid hormone (PTH) levels and subsequent reduction in serum calcium levels [1].
• Saline rehydration followed by furosemide diuresis: This treatment approach has been effective in managing hypercalcemic crisis, but its efficacy in FHH type 3 is unclear [9].

Treatment Challenges:

• Limited therapeutic options: Currently, there are no established treatments for FHH type 3, and management often focuses on symptomatic relief rather than correcting the underlying calcium imbalance.
• Asymptomatic nature: In most cases, FHH type 3 is asymptomatic or presents with minimal symptoms, making treatment unnecessary [7].

Future Directions:

• Investigating new therapeutic targets: Research into the pathophysiology of FHH has identified potential therapeutic targets, such as the CaR and other signaling pathways involved in calcium regulation.
• Development of novel treatments: The development of new calcimimetic agents or other targeted therapies may offer promising treatment options for FHH type 3.

In conclusion, while there is no established treatment for familial hypocalciuric hypercalcemia type 3, research into calcimimetics and other therapeutic approaches holds promise for future management strategies.

Familial hypocalciuric hypercalcemia (FHH) type 3, also known as FHH1, is a condition characterized by mild hypophosphatemia and elevated plasma PTH concentrations. When it comes to differential diagnosis, primary hyperparathyroidism is clinically similar to FHH.

To differentiate between the two conditions, the first step is made by measuring calcium/creatinine clearance. This helps in identifying patients with FHH who have low urine calcium levels, which is a key distinguishing feature from primary hyperparathyroidism.

In addition to this, other differential diagnoses for FHH include:

• Primary hyperparathyroidism: This condition is often clinically similar to FHH and can be differentiated by measuring calcium/creatinine clearance.
• Overactive parathyroid adenoma: This is another important differential diagnosis for FHH, as both conditions can present with mild or no symptoms and elevated serum PTH levels.

It's worth noting that primary hyperparathyroidism is the most common differential diagnosis of familial hypocalciuric hypercalcemia (FHH), particularly in patients with benign FHH (BFHH). However, surgical resection of the hyperplastic parathyroid glands is not typically required for BFHH, unlike in cases of primary PHPT.

References:

• [2] Primary hyperparathyroidism is clinically similar ...
• [3] The first step in the differential diagnosis of FHH and primary hyperparathyroidism is made by calcium/creatinine clearance.
• [5] ... and it is differentiated from primary PHPT by measuring the calcium/creatinine clearance ratio.
• [6] Therefore, primary hyperparathyroidism is the most common differential diagnosis of BFHH.
• [7] Familial hypocalciuric hypercalcemia's main differential diagnosis is an overactive parathyroid adenoma.