familial hypocalciuric hypercalcemia 1

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder that causes high levels of calcium in the blood, but low to moderate levels of calcium in urine. While most people with FHH remain asymptomatic, some may experience mild symptoms.

Common Symptoms:

• Fatigue [4]
• Weakness [13]
• Constipation [7]
• Increased urination [6][7]
• Increased thirst [6][7]
• Loss of appetite [7]

Less Common Symptoms:

• Abdominal pain [7]
• Headaches [4]
• Polyuria (frequent urination) and polydipsia (excessive thirst) [6]
• Skeletal demineralization [2]

It's essential to note that symptoms may vary in severity and can be absent in many cases. In some instances, FHH can lead to more severe conditions, such as tertiary hyperparathyroidism, which is characterized by bone pain, pruritus (itching), fatigue, lethargy, and an increased risk for fractures [14].

In most cases, FHH patients do not require treatment due to the slow and chronic elevation of serum calcium levels, allowing them to adapt to it. However, in some instances, subtotal parathyroidectomy or total parathyroidectomy with autotransplantation may be necessary [14].

Familial Hypocalciuric Hypercalcemia (FHH) can be diagnosed through various diagnostic tests, including:

• Genetic testing: This is the most accurate test for diagnosing FHH. It involves analyzing the CASR gene to detect mutations that cause the condition. Genetic testing can confirm the diagnosis of FHH in most cases, except in rare autoimmune cases [6].
• Blood and urine tests: These tests may be used to rule out other possible causes of hypercalcemia. However, they are not specific for FHH and cannot confirm the diagnosis on their own.
• Imaging studies: Imaging studies such as X-rays, CT scans, or MRI scans may be performed to evaluate the parathyroid glands and other bones in the body.

It's worth noting that a diagnosis of FHH can only be confirmed through genetic testing. The presence of hypercalcemia alone is not sufficient to diagnose FHH, as it can also be caused by other conditions [3].

In addition, a test called CASR gene sequencing may be used to detect mutations in the CASR gene. This test uses next-generation sequencing technology to analyze the entire CASR gene and identify any mutations that may be causing the condition [5].

Based on the provided context, it appears that drug treatment for familial hypocalciuric hypercalcemia (FHH) is not typically recommended.

• According to search result [4], FHH does not usually require treatment, since the condition in most people tends to be asymptomatic or with minimal symptoms.
• Search result [5] also states that FHH is a lifelong benign condition that does not require any treatment or surgery.
• Additionally, search result [11] mentions that no treatment is generally required for FHH, as bone demineralisation and kidney stones are relatively uncommon in the condition.

However, there are some exceptions where calcimimetic therapy may be considered:

• Search result [10] suggests that calcimimetic therapy can potentially be offered to FHH patients, particularly those with hypercalcemia symptoms, serum calcium levels >1 mg/dL (though this is not a universally accepted treatment approach).
• Search result [2] mentions recent case reports describing the use of calcimimetics in treating FHH, although the success of this treatment approach is not clearly defined.

It's worth noting that the primary focus for managing FHH is often patient education and reassurance, with calcimimetic medications (such as bisphosphonates) used in more symptomatic cases, despite not being FDA-approved for FHH.

Familial hypocalciuric hypercalcemia (FHH) is a genetic disorder that causes hypercalcemia, and its differential diagnosis involves identifying conditions that can mimic its symptoms. The main differential diagnoses for FHH are:

• Primary Hyperparathyroidism (PHPT): This is the most common cause of hypercalcemia and can be easily misdiagnosed as FHH due to similar symptoms [3]. PHPT is characterized by an inappropriately normal or elevated level of parathyroid hormone, which can lead to hypercalcemia.
• Overactive Parathyroid Adenoma: This is another condition that can cause hypercalcemia and is often considered a differential diagnosis for FHH [8].
• Primary Hyperparathyroidism (PHPT) with a hyperplastic gland: This is a rare condition where the parathyroid glands are overactive due to a genetic mutation, leading to hypercalcemia. It can be misdiagnosed as FHH due to similar symptoms [6].

The differential diagnosis of FHH and PHPT is made by calcium/creatinine clearance, which helps to distinguish between the two conditions [4]. Additionally, genetic testing can help identify the underlying cause of FHH.

It's worth noting that FHH is a generally asymptomatic genetic disorder, whereas PHPT can present with symptoms such as kidney stones, bone pain, and neuropsychiatric symptoms. Therefore, a thorough clinical evaluation and diagnostic workup are necessary to accurately diagnose and differentiate between these conditions.

References:

[1] Familial hypocalciuric hypercalcemia (FHH) is a generally asymptomatic genetic disorder of phosphocalcic metabolism characterized by lifelong moderate hypercalcemia [2]. [3] Primary Hyperparathyroidism (PHPT) can be easily misdiagnosed as FHH due to similar symptoms [3]. [4] The first step in the differential diagnosis of FHH and primary hyperparathyroidism is made by calcium/creatinine clearance [4]. [6] Primary Hyperparathyroidism (PHPT) with a hyperplastic gland can be misdiagnosed as FHH due to similar symptoms [6]. [8] Overactive Parathyroid Adenoma is another condition that can cause hypercalcemia and is often considered a differential diagnosis for FHH [8].