autosomal dominant hypocalcemia 1

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism, which affects the body's ability to regulate calcium levels.

Key Characteristics:

• Rare disorder: ADH1 is a rare condition, affecting only a small percentage of people.
• Variable degrees of hypocalcemia: People with ADH1 may experience variable degrees of low calcium levels in their blood (hypocalcemia).
• Disproportionately low/normal PTH levels: Despite the low calcium levels, parathyroid hormone (PTH) levels are often disproportionately low or normal.
• Hyperphosphatemia and hypercalciuria: ADH1 is also associated with high phosphate levels in the blood (hyperphosphatemia) and excessive calcium excretion in the urine (hypercalciuria).

Causes:

• Activating variants of the CASR gene: ADH1 is primarily caused by mutations in the calcium-sensing receptor (CASR) gene, which increases the sensitivity of the receptor to calcium.
• Heterozygous activating mutations: These mutations are typically heterozygous, meaning they occur in one copy of the CASR gene.

References:

• [1] Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). [2]
• A rare disorder of calcium homeostasis characterized by variable degrees of hypocalcemia with disproportionately low/normal levels of parathyroid hormone (PTH). [3]
• Autosomal dominant hypocalcemia-1 (HYPOC1) is associated with low or normal serum parathyroid hormone concentrations (PTH). Approximately 50% of patients... [4]

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare genetic disorder characterized by low levels of calcium in the blood, known as hypocalcemia. The signs and symptoms of ADH1 can vary from person to person, but here are some common manifestations:

• Muscle cramps and spasms: These are one of the most common symptoms of ADH1, affecting both hands and feet (carpopedal spasms) [8].
• Paresthesias: This refers to a prickling or tingling sensation in the skin, often felt in the hands and feet [4].
• Tetany: This is a condition characterized by muscle stiffness and spasms, often accompanied by cramps and paresthesias [3].
• Seizures: In some cases, ADH1 can cause seizures, which are a severe symptom that requires immediate medical attention [6][11].
• Hyperphosphatemia: This is a condition where there is an excess of phosphate in the blood, often accompanied by hypomagnesemia (low magnesium levels) [5].
• Nephrocalcinosis: This is a condition where calcium deposits form in the kidneys, which can lead to impaired renal function [5].

It's worth noting that about half of affected individuals with ADH1 have no associated health problems or mild symptoms, while others may experience more severe manifestations [7].

Autosomal dominant hypocalcemia type 1 (ADH1) can be diagnosed through various tests, which are designed to detect the underlying genetic mutation that causes this condition.

• Serum calcium and PTH levels analysis: This is a crucial test for diagnosing ADH1. It involves measuring the levels of calcium and parathyroid hormone (PTH) in the blood. In individuals with ADH1, the serum calcium levels are typically low, while the PTH levels may be normal or elevated ([3][6]).
• Molecular analysis of CASR: This test is used to confirm the diagnosis of ADH1 by analyzing the calcium-sensing receptor (CASR) gene for mutations. It can detect single nucleotide, deletion-insertion, and copy number variants in the CASR gene ([8]).
• Genetic testing: Genetic testing is a comprehensive approach that involves next-generation sequencing to detect mutations in the CASR gene associated with ADH1 ([8][10]).

It's worth noting that genetic testing can also help identify individuals who are carriers of the mutation, even if they do not display symptoms themselves. This information can be useful for family planning and risk assessment ([9]).

Autosomal Dominant Hypocalcemia Type 1 (ADH1) is a rare genetic disorder characterized by low levels of calcium in the blood, known as hypocalcemia. In individuals who require treatment, conventional therapy typically involves administering calcium and vitamin D analogs.

However, this approach can exacerbate the condition by causing an increase in blood calcium levels [2]. Therefore, alternative treatments are being explored to manage ADH1 effectively.

One such investigational drug is encaleret, which has shown promise in restoring normal calcium levels in individuals with ADH1 [9]. Additionally, a calcilytic agent called NPSP795 (SHP635) has been studied for its potential in treating ADH1 by reducing parathyroid hormone activity and increasing calcium levels [8].

In terms of specific treatment protocols, administration of 1-alpha hydroxylated vitamin D is often recommended, with doses ranging from 0.5 to 1.5 micrograms/day, although higher doses may be required in some cases [6]. It's essential for individuals with ADH1 to work closely with their healthcare providers to determine the most effective treatment plan.

References: [2] Conventional therapy for ADH1 patients who require treatment includes calcium and vitamin D analogs; however, the rise in blood calcium exacerbates the condition. [6] Treatment is based on administration of 1-alpha hydroxylated vitamin D (doses ranging from 0.5 to 1.5 micrograms/day, but higher doses are sometimes required). [8] May 7, 2019 — Treatment of Autosomal Dominant Hypocalcemia Type 1 With the Calcilytic NPSP795 (SHP635) ... Public clinical trial registration: http://... [9] Oct 13, 2023 — An investigational drug, encaleret, restored calcium levels in people with autosomal dominant hypocalcemia type 1 (ADH1), a rare genetic disorder.

Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). The differential diagnosis for ADH1 includes various conditions that can present with similar symptoms, such as:

• Hypoalbuminemia: Low levels of albumin in the blood, which can lead to low calcium levels.
• Acute pancreatitis or sepsis: Conditions that can cause a sudden drop in calcium levels.
• Acute kidney injury: Kidney damage that can affect calcium regulation.
• Hyperphosphatemia: High levels of phosphate in the blood, which can contribute to low calcium levels.
• Hypomagnesemia: Low levels of magnesium in the blood, which can also contribute to low calcium levels.
• Hyperparathyroidism: Overactive parathyroid glands that can cause high calcium levels.

It's essential to note that ADH1 is a distinct condition caused by gain-of-function mutations in the CASR gene. A proper diagnosis requires molecular analysis of the CASR gene, as well as serum calcium and PTH level analysis [3][4].

In some cases, differential diagnoses for hypocalcemia in the neonatal period may include genetic hypoparathyroidism, such as the L125P mutation [5]. However, these conditions should be distinguished from ADH1 through proper diagnostic testing.

References: [1] by KL Roszko · 2022 · Cited by 24 — Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium‐sensing receptor gene (CASR). [3] by RI Teleanu · 2023 · Cited by 1 — Although most cases of isolated hypoparathyroidism are sporadic, some exhibit X-linked, autosomal recessive, or autosomal dominant inheritance. [4] by D Goltzman · Cited by 8 — Hypocalcemia has many causes (table 1). It can result from inadequate parathyroid hormone (PTH) secretion, PTH resistance, vitamin D deficiency ... [5] by RI Teleanu · 2023 · Cited by 1 — Hypocalcemia in the neonatal period has a wide differential diagnosis. We present the case of a ...