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Argininosuccinic Aciduria

Disease Details

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Description: Argininosuccinic aciduria is a rare, inherited metabolic disorder that disrupts the urea cycle, leading to the buildup of ammonia and other toxic substances in the blood.
Type: Argininosuccinic aciduria is an inherited disorder that affects the urea cycle. This condition is caused by mutations in the ASL gene. The type of genetic transmission for argininosuccinic aciduria is autosomal recessive.
Signs And Symptoms: Signs and symptoms of argininosuccinic aciduria include:

1. Developmental delay
2. Failure to thrive
3. Hepatomegaly (enlarged liver)
4. Hyperammonemia (elevated ammonia levels in the blood)
5. Vomiting
6. Confusion or lethargy
7. Seizures
8. Intellectual disability
9. Liver dysfunction
10. Brittle hair

This condition is a rare genetic disorder that affects the body's ability to dispose of ammonia, which is a waste product of protein metabolism.
Prognosis: Due to the rarity of the disease, it is hard to estimate mortality rates or life expectancy. One 2003 study which followed 88 cases receiving two different kinds of treatment found that very few persons lived beyond age 20 and none beyond age 30.
Onset: Argininosuccinic aciduria typically presents in infancy or early childhood, often within the first few days of life.
Prevalence: The prevalence of argininosuccinic aciduria is estimated to be around 1 in 70,000 to 1 in 218,000 live births.
Epidemiology: Argininosuccinic aciduria is a rare genetic disorder with an estimated incidence of approximately 1 in 70,000 to 218,000 live births. It is caused by a deficiency of the enzyme argininosuccinate lyase, which is essential in the urea cycle. This disorder is inherited in an autosomal recessive manner.
Intractability: Argininosuccinic aciduria is a rare, inherited metabolic disorder that affects the urea cycle, resulting in the accumulation of argininosuccinic acid. While the condition is challenging to manage and requires lifelong treatment, it is not considered intractable. Management typically involves dietary restrictions to limit protein intake, medications to help remove ammonia from the bloodstream, and supplementation with arginine. Early diagnosis and ongoing care are crucial to improve outcomes and prevent severe complications.
Disease Severity: Argininosuccinic aciduria severity can vary widely among individuals, ranging from mild to severe. In severe cases, symptoms may appear in the neonatal period and can include vomiting, lethargy, seizures, and developmental delay. Early diagnosis and treatment are crucial for better outcomes.
Healthcare Professionals: Disease Ontology ID - DOID:14755
Pathophysiology: Argininosuccinic aciduria, also known as argininosuccinic acidemia, is a rare genetic disorder that affects the urea cycle. The pathophysiology involves a deficiency in the enzyme argininosuccinate lyase (ASL), which is crucial for converting argininosuccinic acid into arginine and fumarate in the urea cycle. This enzymatic deficiency leads to the accumulation of argininosuccinate and ammonia in the blood, causing hyperammonemia. Elevated ammonia levels are toxic and can result in neurological symptoms, liver dysfunction, and, if untreated, can lead to severe impairment or death.
Carrier Status: For argininosuccinic aciduria:

Carrier Status: Individuals who carry a single copy of the mutated gene associated with argininosuccinic aciduria are considered carriers. They typically do not show symptoms but can pass the mutated gene to their offspring. This condition is inherited in an autosomal recessive manner, which means that a child must inherit two copies of the mutated gene (one from each parent) to exhibit the disease. Carriers have one normal copy and one mutated copy of the gene.
Mechanism: Argininosuccinic aciduria is a rare inherited disorder caused by a deficiency of the enzyme argininosuccinate lyase (ASL), which plays a crucial role in the urea cycle. The urea cycle is a biochemical pathway in the liver that converts toxic ammonia into urea for excretion.

**Mechanism:**
In individuals with argininosuccinic aciduria, the deficiency of ASL leads to an accumulation of argininosuccinic acid and ammonia in the blood. The elevated levels of ammonia are toxic to the brain and can cause a range of neurological issues if not properly managed.

**Molecular Mechanisms:**
1. **Gene Mutation**: Argininosuccinic aciduria results from mutations in the ASL gene located on chromosome 7. These mutations can lead to reduced or absent activity of the ASL enzyme.

2. **Enzyme Deficiency**: The ASL enzyme normally catalyzes the conversion of argininosuccinic acid into arginine and fumarate. The loss of function due to gene mutations disrupts this conversion, leading to the accumulation of argininosuccinic acid and a subsequent inability to effectively clear ammonia from the body.

3. **Metabolic Disruption**: The impaired urea cycle causes a buildup of ammonia, which the body cannot convert to urea. This results in hyperammonemia, a condition characterized by high levels of ammonia in the blood, leading to toxic effects on the central nervous system.

4. **Toxic Effects**: Elevated ammonia levels can cause irreversible damage to the brain, manifesting as cognitive impairment, developmental delays, seizures, and in severe cases, coma or death if untreated.

Managing argininosuccinic aciduria typically involves dietary restrictions to limit ammonia production and medications or supplements to enhance alternative pathways for ammonia detoxification. Prompt diagnosis and treatment are crucial to prevent long-term damage.
Treatment: During an acute hyperammonemic episode, oral proteins must be avoided and intravenous (I.V.) lipids, glucose and insulin (if needed) should be given to promote anabolism. I.V. nitrogen scavenging therapy (with sodium benzoate and/or sodium phenylacetate) should normalize ammonia levels, but if unsuccessful, hemodialysis is recommended. Long-term management involves dietary protein restriction as well as arginine supplementation. In those with frequent episodes of metabolic decompensation or with hyperammonemia even when following a protein-restricted diet, daily oral nitrogen scavenging therapy may be successful. Orthotopic liver transplantation offers long-term relief of hyperammonemia but does not seem to sufficiently correct neurological complications. Arterial hypertension can be treated by restoring nitric oxide deficiency
Compassionate Use Treatment: Argininosuccinic aciduria (ASA) is a rare genetic disorder that affects the urea cycle, leading to the accumulation of argininosuccinic acid and related toxic substances in the body. Compassionate use treatments, off-label, or experimental treatments for ASA could include:

1. **L-arginine supplementation**:
- Often used to help reduce ammonia levels in the blood.
- Increases the flux through the urea cycle, promoting the excretion of nitrogen.

2. **Sodium benzoate and sodium phenylbutyrate**:
- These are ammonia scavenging drugs that help to reduce high blood ammonia levels.
- While not specifically approved for ASA, they are frequently used in similar urea cycle disorders.

3. **Gene Therapy**:
- Experimental therapies, such as gene therapy, are being researched to correct the underlying genetic defect in ASA.
- These treatments are still in the trial phase and not widely available.

4. **Liver transplantation**:
- In severe cases, liver transplantation may be considered to provide a functional set of urea cycle enzymes, although this is a major procedure with significant risks and long-term immunosuppression requirements.

These treatments should always be considered and discussed in detail with a healthcare provider who specializes in metabolic disorders.
Lifestyle Recommendations: For individuals with argininosuccinic aciduria, lifestyle recommendations typically include:

1. **Dietary Management**: A low-protein diet specifically tailored to limit the intake of amino acids while ensuring adequate nutrition. Special medical foods and formulas may also be used to help manage protein intake.

2. **Medications**: Prescribed medications such as nitrogen scavengers may help remove excess ammonia from the blood. These can be critical to managing symptoms.

3. **Regular Monitoring**: Frequent monitoring of ammonia levels, amino acids, and other relevant blood markers is essential to prevent metabolic crises.

4. **Emergency Plan**: Having a clear, well-understood emergency plan for managing hyperammonemia, which includes knowing when to seek immediate medical attention, is critical.

5. **Avoidance of Triggers**: Avoiding fasting and conditions that can trigger catabolic stress, such as infections or physical exertion that might increase metabolic demands on the body.

6. **Hydration**: Maintaining optimal hydration to help with metabolic waste removal is often recommended.

7. **Professional Support**: Regular consultations with metabolic specialists, dietitians, and possibly genetic counselors to ensure comprehensive care and support.

These recommendations should be customized to each patient's needs and regularly updated based on their health status and medical advice.
Medication: Argininosuccinic aciduria is a rare genetic disorder that affects the urea cycle. Medications used for management may include:

1. **Ammonul (sodium phenylacetate and sodium benzoate):** Helps to reduce ammonia levels in the blood.
2. **Arginine supplementation:** Helps to detoxify ammonia.
3. **Citrulline:** Sometimes used as an alternative to arginine.
4. **Lactulose:** May be used to help reduce ammonia levels.

Patients typically require a comprehensive treatment plan involving dietary management and regular monitoring by healthcare professionals.
Repurposable Drugs: Argininosuccinic aciduria is a rare inherited disorder that affects the urea cycle. While there are currently no specific "repurposable" drugs officially approved for its treatment, some therapeutic approaches aim to manage symptoms and prevent complications. These methods include:

1. **Nitrogen-Scavenging Agents**: Drugs like sodium benzoate or sodium phenylbutyrate are often used to help reduce the levels of ammonia in the blood.

2. **L-Arginine Supplementation**: Oral or intravenous administration of L-arginine can help improve the urea cycle function and reduce ammonia levels.

Management strategies also include a low-protein diet to minimize ammonia production and nutritional supplements to ensure adequate intake of essential amino acids and calories. Further, liver transplantation has been successful in some severe cases, essentially correcting the enzyme deficiency responsible for the disorder.

Close monitoring by healthcare professionals specializing in metabolic disorders is essential for optimizing treatment and monitoring potential side effects or complications.
Metabolites: Argininosuccinic aciduria is a rare inherited disorder affecting the urea cycle, leading to the accumulation of specific metabolites. These include elevated levels of argininosuccinic acid, arginine, and citrulline in the blood and urine. The accumulation of these metabolites results from a deficiency of the enzyme argininosuccinate lyase.
Nutraceuticals: Argininosuccinic aciduria is a rare genetic disorder affecting the urea cycle. Nutraceuticals for this condition typically focus on reducing ammonia levels in the blood. Common options include:

1. L-citrulline or L-arginine supplements to help bypass the metabolic block.
2. Protein-restricted diets supplemented with essential amino acids to prevent hyperammonemia.
3. Sodium phenylbutyrate or glycerol phenylbutyrate, which help eliminate excess nitrogen.

Nano-based approaches (nan) are still largely experimental and not widely used in clinical practice. However, research is ongoing to explore targeted delivery systems for enzymes or genetic material to correct the underlying metabolic defect.
Peptides: Argininosuccinic aciduria is a rare inherited disorder that affects the urea cycle, which is the body's process for removing toxic ammonia. The condition is caused by a deficiency in the enzyme argininosuccinate lyase. As for "peptides, nan," argininosuccinic aciduria itself does not specifically involve peptides in its definition, but the disruption in the urea cycle can affect the body’s overall protein metabolism, which includes peptides. If you need information on treatment or management involving peptides, more specific context is needed. The term "nan" is unclear in this context; if it refers to nanotechnology, no direct link to this specific disease is readily available in standard medical references.