Neonatal Severe Primary Hyperparathyroidism
Disease Details
Family Health Simplified
- Description
- Neonatal severe primary hyperparathyroidism is a rare genetic disorder causing life-threatening hypercalcemia in infants due to excessive parathyroid hormone release.
- Type
- Neonatal severe primary hyperparathyroidism is an autosomal recessive disorder.
- Signs And Symptoms
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Neonatal severe primary hyperparathyroidism (NSHPT) is a rare and potentially life-threatening condition.
**Signs and Symptoms:**
1. **Hypercalcemia:** Elevated calcium levels in the blood.
2. **Irritability:** Excessive fussiness and difficulty calming the infant.
3. **Poor Feeding:** Difficulty with feeding and poor weight gain.
4. **Hypotonia:** Low muscle tone or floppiness.
5. **Vomiting:** Frequent vomiting episodes.
6. **Constipation:** Difficulty passing stool or infrequent bowel movements.
7. **Polyuria/Polydipsia:** Excessive urination and increased thirst.
8. **Bone Abnormalities:** Symptoms related to bone demineralization, such as fractures or misshapen bones.
9. **Failure to Thrive:** Poor physical growth and development.
If NSHPT is suspected, it requires prompt medical evaluation and intervention due to the risk of severe complications. - Prognosis
- Neonatal severe primary hyperparathyroidism (NSHPT) is a rare and life-threatening condition caused by mutations in the CASR gene. The prognosis for NSHPT is generally poor without prompt intervention. Untreated, it can lead to severe hypercalcemia, bone demineralization, and multi-organ dysfunction. Early diagnosis and treatment, often requiring parathyroidectomy, are crucial for improving outcomes and survival rates.
- Onset
- Neonatal severe primary hyperparathyroidism (NSHPT) typically presents in the first few weeks of life. This rare condition is characterized by extremely high levels of parathyroid hormone (PTH) and hypercalcemia, and it requires prompt medical attention to manage the life-threatening symptoms.
- Prevalence
- The prevalence of neonatal severe primary hyperparathyroidism is extremely rare. Specific figures are not well-documented due to its rarity, but it is considered a rare genetic disorder typically associated with homozygous or compound heterozygous mutations in the CASR gene encoding the calcium-sensing receptor.
- Epidemiology
- Neonatal severe primary hyperparathyroidism (NSHPT) is an extremely rare genetic disorder. It is typically inherited in an autosomal recessive manner and is often associated with mutations in the CASR gene, which encodes the calcium-sensing receptor. The exact prevalence of NSHPT is not well-documented due to its rarity, but it is considered a very uncommon condition in the general population. Cases are often reported in populations with higher rates of consanguinity.
- Intractability
- Neonatal severe primary hyperparathyroidism (NSPH) is considered intractable as it typically requires urgent medical intervention. It often does not respond well to standard medical treatments and usually necessitates surgical intervention, such as a parathyroidectomy, to manage the condition effectively and prevent life-threatening complications.
- Disease Severity
- Neonatal severe primary hyperparathyroidism (NSPHPT) is a life-threatening condition if left untreated. It typically presents with severe hypercalcemia, leading to symptoms such as poor feeding, hypotonia, respiratory distress, and failure to thrive in neonates. Early diagnosis and intervention, often surgical removal of the overactive parathyroid glands, are crucial to prevent serious complications, including multi-organ damage and death.
- Pathophysiology
- Neonatal severe primary hyperparathyroidism is a rare and life-threatening condition characterized by markedly elevated serum calcium levels due to hypersecretion of parathyroid hormone (PTH). The pathophysiology typically involves mutations in the CASR gene, which encodes the calcium-sensing receptor (CaSR) crucial for regulating PTH secretion. Loss-of-function mutations in CASR impair the receptor’s ability to sense extracellular calcium, leading to unregulated PTH secretion, hypercalcemia, and increased bone resorption. This condition can result in severe complications including bone demineralization, fractures, nephrocalcinosis, and failure to thrive in neonates.
- Carrier Status
- Neonatal severe primary hyperparathyroidism (NSHPT) is an autosomal recessive disorder. This means that carriers of the mutation (individuals with one normal and one mutated gene) typically do not exhibit symptoms but can pass the mutated gene to their offspring. For a child to be affected with NSHPT, they must inherit two mutated copies of the gene, one from each carrier parent.
- Mechanism
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Neonatal severe primary hyperparathyroidism (NSHPT) is a rare, life-threatening disorder characterized by excessive secretion of parathyroid hormone (PTH) from the parathyroid glands, leading to severe hypercalcemia.
**Mechanism:**
NSHPT arises due to unchecked proliferation and activity of the parathyroid glands, which results in the excessive release of PTH. This hormone increases calcium levels in the blood by:
1. Increasing calcium reabsorption in the kidneys.
2. Enhancing calcium release from bones.
3. Increasing intestinal calcium absorption through its effect on vitamin D metabolism.
**Molecular Mechanisms:**
The condition typically results from mutations in the calcium-sensing receptor (CaSR) gene. The CaSR is a G-protein-coupled receptor found in the parathyroid glands and the kidneys, which plays a crucial role in maintaining calcium homeostasis by regulating PTH secretion. Mutations in the CaSR gene impair the ability of parathyroid cells to sense extracellular calcium levels properly, leading to inappropriate PTH release despite high serum calcium levels. This dysregulation is the primary molecular mechanism driving the pathophysiology of NSHPT. - Treatment
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Neonatal severe primary hyperparathyroidism is a rare genetic disorder typically caused by mutations in the calcium-sensing receptor (CASR) gene. It is characterized by hypercalcemia and elevated parathyroid hormone (PTH) levels. Treatment often involves:
1. **Surgical Intervention**: Total parathyroidectomy (removal of all parathyroid glands) is the definitive treatment to control severe hypercalcemia and reduce PTH levels. Immediate surgical correction is often necessary due to the life-threatening nature of the condition.
2. **Medical Management**: Before surgery, medications like intravenous saline, diuretics (e.g., furosemide), bisphosphonates, and calcimimetics may be used to manage hypercalcemia. These medications help lower serum calcium levels but are usually temporary measures.
Early diagnosis and treatment are crucial to prevent complications such as neurological damage, nephrocalcinosis, and other end-organ effects. - Compassionate Use Treatment
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Neonatal severe primary hyperparathyroidism (NSHPT) is a rare and life-threatening condition caused by mutations in the calcium-sensing receptor (CASR) gene, leading to severe hypercalcemia. For treatment, the primary approach is often surgical, specifically a total parathyroidectomy.
For compassionate use or off-label treatments, cinacalcet, a calcimimetic agent, has been used in some cases. Cinacalcet helps to decrease parathyroid hormone (PTH) levels and serum calcium levels by enhancing the sensitivity of the CASR to extracellular calcium. While not FDA-approved specifically for NSHPT, it has shown effectiveness in managing hypercalcemia in some patients who are not immediate candidates for surgery or as a bridge to surgery.
Experimental treatments and ongoing clinical trials may also explore new therapeutic approaches. These treatments aim to address the genetic underpinnings of the disease or offer new avenues for managing hypercalcemia and associated symptoms. - Lifestyle Recommendations
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Neonatal Severe Primary Hyperparathyroidism (NSPHPT) is a rare and life-threatening condition often requiring urgent medical intervention. Given its severity and the need for specialized treatment, lifestyle recommendations are generally secondary to immediate medical care. However, some supportive care recommendations might include:
1. **Monitoring and Support**: Continuous medical supervision to monitor calcium levels and overall health.
2. **Hydration**: Ensure proper hydration to help manage calcium levels in the blood.
3. **Specialized Diet**: Under medical advice, maintaining a diet low in calcium and vitamin D might be suggested.
4. **Medical Compliance**: Adhering strictly to the prescribed medications and therapies.
5. **Regular Follow-ups**: Frequent medical check-ups to adjust treatment plans as necessary.
It is crucial to consult a healthcare professional for personalized guidance and treatment planning. - Medication
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Neonatal severe primary hyperparathyroidism is a rare genetic condition affecting calcium regulation. The primary treatment is surgical removal of the overactive parathyroid glands (parathyroidectomy). Medications are generally used to manage symptoms preoperatively or when surgery is not immediately possible. These may include:
1. **Intravenous Bisphosphonates**: To lower serum calcium levels.
2. **Calcitonin**: To inhibit bone resorption and reduce calcium levels.
3. **Hydration with Saline**: To promote calcium excretion through the kidneys.
4. **Medications to manage other associated symptoms and complications**: For example, diuretics like furosemide to enhance calcium excretion.
Early and prompt treatment is critical to manage this life-threatening condition effectively. - Repurposable Drugs
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Neonatal severe primary hyperparathyroidism (NSPHT) is a rare genetic disorder typically caused by homozygous or compound heterozygous mutations in the calcium-sensing receptor (CASR) gene. Treatment often involves addressing the severe hypercalcemia.
Repurposable drugs that have been reported or considered for managing hypercalcemia in NSPHT include:
1. **Bisphosphonates**: These drugs, such as pamidronate and zoledronic acid, can help inhibit bone resorption and decrease calcium levels.
2. **Calcimimetics**: Cinacalcet is a calcimimetic agent that can enhance the sensitivity of the calcium-sensing receptor and reduce parathyroid hormone (PTH) levels and serum calcium.
3. **Loop Diuretics**: Furosemide can promote calcium excretion in the urine but must be used with adequate hydration and monitoring of electrolytes.
These treatments are generally supportive and may be used as temporizing measures until more definitive management, such as total parathyroidectomy, can be performed. - Metabolites
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Neonatal severe primary hyperparathyroidism (NSHPT) is characterized by significantly elevated levels of calcium in the blood (hypercalcemia) and elevated parathyroid hormone (PTH) levels. Key metabolites involved in this condition include:
1. **Serum calcium**: Elevated
2. **Parathyroid hormone (PTH)**: Elevated
3. **Serum phosphorus**: Often decreased
4. **1,25-dihydroxyvitamin D (calcitriol)**: May be normal or elevated
5. **Alkaline phosphatase**: Elevated
These metabolites are usually measured to diagnose and manage NSHPT. - Nutraceuticals
- There are no known nutraceuticals for the treatment of neonatal severe primary hyperparathyroidism (NSPHPT). This condition is typically managed with medical and surgical interventions. Treatment often involves hydration, medications to lower calcium levels, and in severe cases, parathyroidectomy. Nutraceuticals have not been proven effective for this rare and severe condition.
- Peptides
- Neonatal severe primary hyperparathyroidism (NSHPT) is a rare, life-threatening condition characterized by excessive secretion of parathyroid hormone (PTH), leading to hypercalcemia. Peptides like parathyroid hormone-related protein (PTHrP) can be involved, as they share similar biological activities with PTH. Managing this condition often necessitates interventions such as parathyroidectomy or medical treatments to manage calcium levels.