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Citrullinemia Type I

Disease Details

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Description: Citrullinemia type I is a rare genetic disorder characterized by the inability to convert ammonia and other nitrogen compounds into urea due to a deficiency of the enzyme argininosuccinate synthase.
Type: Citrullinemia Type I is primarily transmitted through an autosomal recessive pattern.
Signs And Symptoms: Citrullinemia Type I is a rare genetic disorder that affects the urea cycle, leading to an accumulation of ammonia in the blood. The signs and symptoms can vary but often include:

- Lethargy
- Vomiting
- Seizures
- Poor feeding
- Irritability
- Developmental delays
- Respiratory distress
- Enlarged liver

In severe cases, especially in newborns, it can lead to life-threatening complications if not treated promptly.
Prognosis: Citrullinemia Type I is a rare genetic disorder affecting the urea cycle, leading to an accumulation of ammonia in the blood. The prognosis for individuals with Citrullinemia Type I can vary widely depending on the severity of the condition and the promptness of diagnosis and treatment. Without early intervention, it can be life-threatening, particularly in newborns. However, with appropriate management — including dietary modifications, medications to manage ammonia levels, and sometimes liver transplantation — individuals can lead relatively normal lives. Early and ongoing treatment plays a crucial role in improving outcomes.
Onset: Citrullinemia Type I typically has its onset in newborns, usually within the first few days of life. The condition is characterized by a deficiency of the enzyme argininosuccinate synthetase, leading to an accumulation of ammonia and other toxic substances in the blood. Symptoms can include vomiting, lethargy, seizures, and poor feeding. If not treated promptly, it can lead to serious complications, including intellectual disability and even death.
Prevalence: Citrullinemia Type I is a rare genetic disorder with a prevalence estimated at 1 in 57,000 to 1 in 250,000 live births.
Epidemiology: Citrullinemia type I is a rare genetic disorder predominantly found in newborns. The epidemiology of citrullinemia type I shows that it has an estimated incidence of approximately 1 in 57,000 to 250,000 live births globally. The condition is caused by mutations in the ASS1 gene and follows an autosomal recessive pattern of inheritance. It tends to occur more frequently in certain populations, such as those in Japan and Saudi Arabia, due to consanguinity.
Intractability: Citrullinemia type I, also known as classic citrullinemia, is typically considered intractable without medical intervention. Management involves lifelong dietary modifications and medications to control ammonia levels in the blood. If untreated, the disease can lead to severe complications, including neurological damage and death. Early diagnosis and treatment are crucial for improving the prognosis and quality of life for affected individuals.
Disease Severity: Citrullinemia Type I is a severe inherited disorder that typically manifests in the neonatal period, often within the first few days of life. The severity of the disease can vary, but it often leads to serious complications such as hyperammonemia, which can result in lethargy, poor feeding, vomiting, seizures, and potentially life-threatening conditions if not treated promptly. Some milder forms can present later in infancy or childhood with less acute symptoms.
Pathophysiology: Citrullinemia Type I, also known as classic citrullinemia, is an inherited metabolic disorder caused by a deficiency of the enzyme argininosuccinate synthase (ASS1). This enzyme is crucial in the urea cycle, which detoxifies ammonia by converting it to urea for excretion. A deficiency in ASS1 leads to the accumulation of ammonia and other toxic substances in the blood. Elevated ammonia levels can cause severe neurological symptoms and, if untreated, can result in brain damage, coma, or death.
Carrier Status: Citrullinemia Type I is an autosomal recessive disorder. Carrier status means that an individual has one copy of the mutated gene but does not usually show symptoms of the disease. Carriers can pass the mutated gene to their offspring. If both parents are carriers, their children have a 25% chance of having the disease, a 50% chance of being carriers themselves, and a 25% chance of neither having the disease nor being carriers.

"Nan" isn't clear in this context, so no specific information can be provided about that term. If you provide more context or clarify what "nan" refers to, I may be able to assist further.
Mechanism: Citrullinemia Type I is a rare genetic disorder that affects the urea cycle, the body's process for removing ammonia from the bloodstream. The mechanism is primarily due to mutations in the ASS1 gene, which encodes the enzyme argininosuccinate synthetase.

**Molecular Mechanisms:**
1. **Gene Mutation:** Mutations in the ASS1 gene result in a deficient or nonfunctional argininosuccinate synthetase enzyme.
2. **Enzyme Deficiency:** The dysfunctional enzyme impairs the conversion of citrulline and aspartate into argininosuccinate, an essential step in the urea cycle.
3. **Ammonia Accumulation:** Since the urea cycle cannot proceed normally, ammonia accumulates in the blood, leading to hyperammonemia.
4. **Disrupted Metabolism:** High levels of ammonia are toxic to the brain and other tissues, causing neurological symptoms and potentially life-threatening complications.

Thus, the disease is characterized by an inability to effectively detoxify ammonia due to a critical defect in the urea cycle's enzymatic process.
Treatment: Citrullinemia Type I (CTLN1) is a urea cycle disorder that can lead to severe hyperammonemia.

Treatment involves:
1. Acute Management:
- Reduction of ammonia levels through medications like sodium phenylbutyrate and sodium benzoate.
- Intravenous arginine supplementation to promote the urea cycle.
- Hemodialysis may be necessary to rapidly reduce plasma ammonia levels.

2. Long-term Management:
- Dietary restrictions to limit protein intake.
- Lifelong supplementation with arginine and other amino acids.
- Liver transplantation can be considered in severe cases.

There is currently no widely recognized treatment involving nanotechnology (nan) for CTLN1.
Compassionate Use Treatment: Citrullinemia Type I (CTLN1) is a rare genetic disorder caused by a deficiency of the enzyme argininosuccinate synthetase, which is crucial in the urea cycle.

### Compassionate Use Treatments:
Compassionate use, also known as expanded access, involves making investigational drugs available to patients with serious diseases or conditions. These treatments are typically allowed when no comparable or satisfactory alternative therapy options are available.

### Off-Label or Experimental Treatments:
1. **Sodium Phenylbutyrate**: This drug is used off-label to help remove excess ammonia from the blood by providing an alternate pathway for nitrogen excretion through the kidneys.
2. **Sodium Benzoate**: Another off-label treatment, it also helps to reduce ammonia levels by aiding its excretion.
3. **Carbamylglutamate**: Off-label use of this drug may help activate the urea cycle and reduce ammonia levels.
4. **Gene Therapy**: Currently experimental, gene therapy aims to correct the underlying genetic defect by introducing functional copies of the gene responsible for the enzyme deficiency.
5. **Liver Transplant**: In severe cases, a liver transplant may be considered as it can help to provide the missing enzyme and correct the metabolic defect.
6. **SiRNA-based therapies**: These are in experimental stages and aim to silence specific genes that contribute to the disease process.

Patients considering any off-label or experimental treatments should consult their healthcare providers for the most appropriate and updated therapeutic options.
Lifestyle Recommendations: For Citrullinemia Type I, lifestyle recommendations typically include:

1. **Dietary Management**:
- Follow a low-protein diet to minimize the production of ammonia.
- Use special medical formulas and supplements to ensure adequate nutrition while controlling protein intake.
- Regularly monitor amino acid levels in the blood.

2. **Medication**:
- Take prescribed medications, such as sodium phenylbutyrate or sodium benzoate, to help remove excess ammonia from the blood.

3. **Routine Monitoring**:
- Regularly check blood ammonia levels to prevent hyperammonemia.
- Frequent visits to healthcare specialists, including metabolic specialists and nutritionists.

4. **Emergency Plan**:
- Have an action plan for managing hyperammonemia, which may include emergency hospital visits for intravenous treatments to lower ammonia levels.

5. **Avoiding Triggers**:
- Prevent prolonged fasting and ensure regular, balanced meals.
- Avoid strenuous physical activities that may increase catabolism.

6. **Education and Support**:
- Seek genetic counseling for family planning.
- Engage with support groups for emotional and practical advice.

These recommendations are essential to manage the condition effectively and prevent complications. Always consult with healthcare providers for personalized management.
Medication: Citrullinemia type I is a rare genetic disorder that leads to an accumulation of ammonia in the blood due to a deficiency in the enzyme argininosuccinate synthetase. Medications used in the management of citrullinemia type I include:

1. **Ammonia Scavengers**: These help reduce ammonia levels in the blood. Common medications include:
- Sodium phenylbutyrate
- Sodium benzoate

2. **Arginine Supplementation**: As arginine is often deficient in patients, it is supplemented to help drive the urea cycle forward.

Treatment plans often involve a combination of medications, dietary management, and regular monitoring of ammonia levels. In severe cases, liver transplantation may be considered.
Repurposable Drugs: As of recent studies and information, there are no widely recognized or specific repurposable drugs for Citrullinemia Type I. It's primarily managed through dietary restrictions, supplements, and ammonia scavenging drugs like sodium phenylbutyrate or sodium benzoate.
Metabolites: Citrullinemia Type I is a rare genetic disorder characterized by the accumulation of ammonia and other toxic substances in the blood. This is due to a deficiency of the enzyme argininosuccinate synthetase, which plays a critical role in the urea cycle. In Citrullinemia Type I, the following metabolites are elevated:

1. **Citrulline:** Elevated levels of citrulline in the blood and urine are a hallmark of the disorder.
2. **Ammonia:** Hyperammonemia, or high levels of ammonia in the blood, is a key clinical feature.
3. **Glutamine:** Increased levels of glutamine may also be observed due to its role in ammonia detoxification.

Managing these elevated metabolites typically involves dietary restrictions and medications that help to remove excess ammonia from the body.
Nutraceuticals: For Citrullinemia Type I, there are no established nutraceuticals specifically designed for this condition. Citrullinemia Type I is a rare genetic disorder affecting the urea cycle, leading to an accumulation of ammonia in the blood. Management typically involves dietary restrictions to limit ammonia production, supplementation with arginine, and medications such as sodium phenylbutyrate or sodium benzoate to help remove excess ammonia. Nutraceuticals are not a standard treatment for this condition.
Peptides: In the context of Citrullinemia Type I, the term "peptides" typically refers to short chains of amino acids that might be affected due to the enzyme deficiency in the urea cycle. Citrullinemia Type I is caused by a deficiency of the enzyme argininosuccinate synthetase, which leads to the accumulation of ammonia and other toxic substances in the blood.

"NAN" doesn't provide enough context, but if you are referring to blood urea nitrogen (often abbreviated as BUN), elevated levels of BUN are commonly seen in patients with Citrullinemia Type I due to impaired ammonia conversion into urea for excretion.