familial isolated hypoparathyroidism

Familial isolated hypoparathyroidism (FIH) is a rare genetic disorder characterized by severe hypocalcemia, seizures, hyperphosphatemia, and impaired secretion of the parathyroid hormone (PTH). The clinical presentation varies widely from mild disease with tingling paresthesias and muscle cramps to more severe disease that may cause significant morbidity.

Common signs and symptoms:

• Severe hypocalcemia [2]
• Hyperphosphatemia [3]
• Impaired secretion of parathyroid hormone (PTH) [3]
• Muscle cramps and weakness [2]
• Tingling paresthesias [7]
• Stiff gait [9]

Rare but possible symptoms:

• Seizures [3]
• Parkinsonism, dystonia, hemiballismus, and oculogyric crises in approximately 5% of patients [6]

It's essential to note that the signs and symptoms can vary widely among individuals with FIH. Some patients may have virtually no complaints, while others may experience more severe manifestations.

References: [1] Not applicable (no relevant information found) [2] Aug 14, 2024 — Hypocalcemia can cause a variety of symptoms including weakness, muscle cramps, excessive nervousness, headaches, and/or uncontrollable ... [3] A rare genetic endocrine disease characterized by severe hypocalcemia, seizures, hyperphosphatemia, and impaired secretion of the parathyroid hormone (PTH) [6] May 20, 2024 — Parkinsonism, dystonia, hemiballismus, and oculogyric crises may occur in approximately 5% of patients with idiopathic hypoparathyroidism. [7] Dr. Clarke explains: "The clinical presentation varies widely from mild disease with tingling paresthesias and muscle cramps to more severe disease that may ... [9] Clinical signs may also include a stiff gait. Blood work reveals low calcium, typically high phosphorus, and low or inappropriately normal parathyroid hormone ( ...

Diagnostic Tests for Familial Isolated Hypoparathyroidism

Familial isolated hypoparathyroidism (FIH) is a rare genetic disorder that affects the production of parathyroid hormone (PTH), leading to low calcium levels in the blood. Diagnosing FIH requires a combination of clinical evaluation, patient history, and specialized tests.

Blood Tests

The diagnosis of FIH begins with blood tests that measure various parameters, including:

• Intact parathyroid hormone (PTH)
• Calcium
• Phosphorous
• Magnesium

These tests help identify characteristic symptoms and confirm the presence of low PTH levels ([1], [9]).

Genetic Testing

In addition to blood tests, genetic testing is also essential for diagnosing FIH. This involves analyzing the GCM2 gene, which is associated with 42% of isolated hypoparathyroidism cases ([3]). Genetic testing can confirm the presence of mutations in the GCM2 gene and rule out other potential causes of low PTH levels.

Other Diagnostic Tests

While not directly related to FIH diagnosis, other tests may be performed to rule out differential diagnoses. These include:

• Autoimmune hypoparathyroidism
• Autoimmune polyendocrinopathy type 1
• Syndromes with hypoparathyroidism as a feature (e.g., 22q11.2 deletion syndrome) ([12])

Clinical Evaluation

A thorough clinical evaluation, including a detailed patient history and physical examination, is also crucial for diagnosing FIH. This helps identify characteristic symptoms, such as tingling in the lips, fingers, and toes, and muscle aches or cramps ([13]).

In summary, diagnosing familial isolated hypoparathyroidism requires a combination of blood tests, genetic testing, and clinical evaluation to confirm low PTH levels and rule out other potential causes.

Treatment Options for Familial Isolated Hypoparathyroidism (FIH)

Familial isolated hypoparathyroidism (FIH) is a rare genetic disorder characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH). While there is no cure for FIH, various treatment options are available to manage the symptoms and improve quality of life.

Standard Therapy

Calcium and vitamin D are the standard therapy for managing hypoparathyroidism in general, including FIH. However, this approach may not be sufficient to address the underlying genetic defect in FIH (1). In some cases, hormone replacement therapy with recombinant human parathyroid hormone (rhPTH(1-84)) may be considered (3).

Recombinant Human Parathyroid Hormone (rhPTH)

The use of rhPTH has been shown to be effective in managing hypoparathyroidism, including FIH. The goals of therapy with rhPTH are to minimize or eliminate the use of active vitamin D, reduce supplemental calcium to 500 mg daily, and maintain normal serum calcium levels (5). However, it's worth noting that rhPTH is an expensive drug, which may limit its accessibility (6).

Other Treatment Options

While there is no long-term treatment or cure for FIH, symptomatic treatment with supplementary calcium and active vitamin D can help manage the symptoms. In some cases, a genetic variant has been identified as the cause of EFIH, and a DNA test is available to help diagnose this condition (8).

Prognosis

If well-treated, life expectancy in individuals with FIH is normal, but quality of life may be affected by the symptoms of hypoparathyroidism. Management consists of symptomatic treatment with supplementary calcium and active vitamin D.

References:

1. [4] - FIH is a rare heterogeneous group of metabolic disorders characterized by abnormal calcium metabolism due to deficient secretion of parathormone (PTH).
2. [3] - Calcium and vitamin D are the standard therapy for the management of hypoparathyroidism, with hormone replacement [recombinant human PTH(1-84)] ...
3. [5] - The goals of therapy with rhPTH (1-84) are to minimize or eliminate the use of active vitamin D, to reduce supplemental calcium to 500 mg daily, and to maintain ...
4. [6] - Approval of the recombinant human parathyroid hormone rhPTH(1-84), currently an expensive drug, for treatment of hypoparathyroidism has stimulated research ...
5. [8] - Oct 20, 2020 — There is no long-term treatment or cure for EFIH. A genetic variant has been identified that causes EFIH. A DNA test is available to help ...

Familial isolated hypoparathyroidism (FIH) is a rare genetic disorder characterized by isolated hypoparathyroidism, which can be challenging to diagnose due to its similarity with other conditions. The differential diagnosis for FIH includes:

• Autoimmune polyendocrinopathy type 1 (APS-1): A rare autosomal recessive disorder that affects multiple endocrine glands and the skin.
• 22q11.2 deletion syndrome: A genetic disorder characterized by a deletion in chromosome 22, which can lead to hypoparathyroidism among other features.
• Autoimmune isolated hypoparathyroidism: A rare condition where hypoparathyroidism is associated with other autoimmune endocrine diseases.
• Post-surgical hypoparathyroidism: A condition that occurs after neck surgery, leading to damage or removal of the parathyroid glands.
• Metastatic carcinoma: Cancer that has spread to the parathyroid glands, causing hypoparathyroidism.
• Neonatal hypoparathyroidism: A rare condition where hypoparathyroidism is present at birth.
• Maternal hyperparathyroidism: A condition where the mother has an overactive parathyroid gland, which can affect the fetus.

These conditions can be ruled out through a combination of clinical evaluation, laboratory tests, and genetic analysis. For example:

• PTH measurement helps differentiate hypoparathyroidism from other disorders of low blood calcium [7].
• The presence or personal history of other autoimmune conditions may indicate an autoimmune basis for a patient's hypoparathyroidism [4].
• Genetic testing can identify mutations in the GCM2 gene, which are