autosomal dominant hypocalcemia

Autosomal dominant hypocalcemia (ADH) is a rare disorder of calcium homeostasis characterized by low levels of calcium in the blood, often accompanied by abnormal parathyroid hormone (PTH) levels.

Key Features:

• Low or normal serum PTH concentrations [5]
• Hypocalcemia (low calcium levels) with disproportionately low/normal PTH levels [3]
• Hyperphosphatemia (high phosphate levels) and hypercalciuria (excessive calcium in the urine) [4]

Causes:

ADH is caused by heterozygous activating mutations in the calcium-sensing receptor gene (CASR), which increases the sensitivity of the CASR to calcium, leading to an inappropriate suppression of PTH secretion [6][7].

Symptoms:

• Muscle spasms in the hands and feet (carpopedal spasms) [1]
• Muscle cramping
• Other symptoms may include weakness, fatigue, and neuropsychiatric manifestations.

It's worth noting that ADH is a rare condition, and its diagnosis can be challenging. A comprehensive medical evaluation, including laboratory tests and genetic analysis, is necessary to confirm the diagnosis.

References:

[1] Feb 1, 2015 — The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, ...

[3] A rare disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with disproportionately low/normal levels of parathyroid hormone (PTH) ...

[4] by KL Roszko · 2016 · Cited by 77 — Biochemical hallmarks of AHD1 are hypocalcemia, which is typically mild to moderate, hyperphosphatemia, hypercalciuria, and inappropriately low ...

[5] by KL Roszko · 2022 · Cited by 24 — Autosomal dominant hypocalcemia-1 (HYPOC1) is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% ...

[6] by KL Roszko · 2016 · Cited by 77 — Autosomal dominant hypocalcemia (ADH) type 1 is caused by heterozygous activating mutations in the CASR which increase the sensitivity of the CASR to calcium, leading to an inappropriate suppression of PTH secretion.

[7] by KL Roszko · 2020 · Cited by 24 — ABSTRACT. Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene.

Autosomal dominant hypocalcemia (ADH) is a rare genetic disorder characterized by low levels of calcium in the blood, known as hypocalcemia. The symptoms of ADH can vary in severity and may include:

• Muscle spasms: Muscle cramps or spasms in the hands and feet are common features of ADH [2][8].
• Tetany: This is a condition characterized by muscle stiffness or rigidity, often accompanied by spasms [5].
• Paresthesia: A prickling or tingling sensation in the skin can occur due to nerve damage caused by low calcium levels [8].
• Seizures: In severe cases of ADH, seizures may occur due to the significant drop in calcium levels [6][9].
• Bone/joint pain: Some individuals with ADH may experience bone or joint pain as a result of the disorder [1][6].
• Fatigue and brain fog: Moderate symptom burden can include fatigue and brain fog, which can significantly impact daily life [6].

It's essential to note that approximately 50% of patients have mild or asymptomatic hypocalcemia, while about 10% may experience severe symptoms like seizures [7]. The severity and presentation of ADH can vary greatly among individuals.

References: [1] KL Roszko · 2022 [2] Feb 1, 2015 [5] by D Goltzman · Cited by 16 [6] by KL Roszko · 2020 · Cited by 24 [7] Approximately 50% of patients have mild or asymptomatic hypocalcemia; about 50% have paresthesias, carpopedal spasm, and seizures; about 10% have hypercalciuria ... [8] The most common features of autosomal dominant hypocalcemia include muscle spasms in the hands and feet (carpopedal spasms) and muscle cramping, prickling or ... [9] by MS Elston · 2022 · Cited by 5

Autosomal dominant hypocalcemia (ADH) is a rare genetic disorder characterized by low levels of calcium in the blood. Diagnostic tests for ADH are crucial to confirm the diagnosis and rule out other conditions that may cause similar symptoms.

Diagnostic Tests:

• Serum Calcium and PTH Levels: The first step in diagnosing ADH is to measure serum calcium and parathyroid hormone (PTH) levels. This test can help identify low calcium levels and rule out other conditions that may cause hypocalcemia [1].
• Molecular Analysis of CASR Gene: Molecular analysis of the CASR gene, which is associated with ADH, can confirm the diagnosis. This test detects single nucleotide, deletion-insertion, and copy number variants in the CASR gene [7][8].
• Genetic Testing Registry: The Genetic Testing Registry (GTR) provides information on genetic tests available for ADH, including molecular analysis of the CASR gene [6].

Clinical Molecular Genetics Test:

A clinical molecular genetics test is available for ADH, which utilizes next-generation sequencing to detect single nucleotide, deletion-insertion, and copy number variants in the CASR gene. This test can help confirm the diagnosis and identify genetic mutations associated with ADH [5][7][8].

Differential Diagnosis:

It's essential to consider differential diagnoses when evaluating patients with suspected ADH. A comprehensive evaluation of serum calcium and PTH levels, along with molecular analysis of the CASR gene, can help rule out other conditions that may cause similar symptoms [3][4].

In conclusion, diagnostic tests for autosomal dominant hypocalcemia include serum calcium and PTH levels, molecular analysis of the CASR gene, and clinical molecular genetics testing. These tests can help confirm the diagnosis and identify genetic mutations associated with ADH.

References: [1] Context 2 [3] Context 3 [4] Context 3 [5] Context 5 [6] Context 6 [7] Context 7 [8] Context 8

Autosomal dominant hypocalcemia (ADH) type 1 is a rare genetic disorder characterized by an imbalance of calcium in the blood and urine, as well as abnormally low levels of parathyroid hormone. The treatment for ADH1 typically involves managing symptoms and correcting the underlying calcium imbalance.

Current Standard of Care

The current standard of care for patients with ADH1 includes oral calcium and/or active vitamin D supplements that are typically administered to correct the calcium imbalance [8][9]. These supplements can help increase blood calcium levels and reduce the risk of complications associated with hypocalcemia.

Investigational Drugs

Recent studies have explored the use of investigational drugs, such as encaleret, which has shown promise in restoring calcium levels in people with ADH1 [4][12]. Encaleret works by inhibiting the action of parathyroid hormone, thereby reducing calcium excretion and increasing blood calcium levels.

Other Treatment Options

In some cases, treatment may also involve addressing underlying conditions that contribute to hypocalcemia. For example, patients with ADH1 who have low levels of parathyroid hormone may require additional therapy to correct this deficiency [7].

Key Points:

• Oral calcium and/or active vitamin D supplements are the current standard of care for ADH1.
• Investigational drugs like encaleret show promise in restoring calcium levels in people with ADH1.
• Treatment may also involve addressing underlying conditions that contribute to hypocalcemia.

References:

[4] by RI Gafni · 2023 · Cited by 7 — We treated 13 adults with ADH1 (caused by nine different CASR variants) with encaleret, an investigational oral calcilytic, in an open-label, phase 2b study. [8] Oct 10, 2023 — The current standard of care for patients with ADH1 includes oral calcium and/or active vitamin D supplements that are typically administered to correct the calcium imbalance. [9] Oct 10, 2023 — An investigational drug, encaleret, restored calcium levels in people with autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder marked by an imbalance of calcium in the blood and urine, as well as abnormally low levels of parathyroid hormone. [12] An investigational drug, encaleret, restored calcium levels in people with autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder marked by an imbalance of calcium in the blood and urine, as well as abnormally low levels of parathyroid hormone.

Autosomal dominant hypocalcemia, also known as autosomal dominant hypoparathyroidism, is a rare genetic disorder characterized by low levels of calcium in the blood (hypocalcemia). The differential diagnosis for this condition involves identifying other possible causes of hypocalcemia that may mimic or coexist with autosomal dominant hypocalcemia.

Possible Causes:

• Hypoparathyroidism: A condition where the parathyroid glands do not produce enough parathyroid hormone (PTH), leading to low calcium levels in the blood.
• Vitamin D deficiency: A lack of vitamin D can lead to impaired calcium absorption, resulting in hypocalcemia.
• Pseudohypoparathyroidism: A rare genetic disorder that affects the regulation of PTH and calcium metabolism.
• Familial hypocalciuric hypercalcemia (FHH): A rare genetic disorder characterized by high levels of calcium in the blood, despite low levels of PTH.

Other Conditions to Consider:

• Intracranial bleeding: Bleeding in the brain can lead to hypocalcemia due to the release of calcium-binding proteins.
• Narcotic withdrawal: Withdrawal from narcotics can cause hypocalcemia due to changes in calcium metabolism.
• Rickets, osteomalacia, or rachitis: Conditions characterized by softening of bones due to vitamin D deficiency, which can lead to hypocalcemia.

Key Points:

• Autosomal dominant hypocalcemia is a rare genetic disorder that affects the regulation of PTH and calcium metabolism.
• The differential diagnosis for this condition involves identifying other possible causes of hypocalcemia that may mimic or coexist with autosomal dominant hypocalcemia.
• A comprehensive evaluation, including laboratory tests and molecular analysis, is necessary to confirm the diagnosis.

References:

[2] Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). [3] Diagnosis is made through analysis of serum calcium and PTH levels. Molecular analysis of CASR followed by GNA11 confirms diagnosis. Differential diagnosis. [9] We therefore propose flowcharts for the differential diagnosis of hypocalcemia and hypoparathyroidism, especially PTH-deficient hypoparathyroidism in which many ...