Argininosuccinate Synthetase Deficiency
Disease Details
Family Health Simplified
- Description
- Argininosuccinate synthetase deficiency is a rare genetic disorder characterized by the body's inability to properly process nitrogen, leading to the accumulation of ammonia in the blood.
- Type
- Argininosuccinate synthetase deficiency is an autosomal recessive disorder.
- Signs And Symptoms
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Argininosuccinate synthetase deficiency, also known as citrullinemia type I, is a disorder that affects the urea cycle, leading to the accumulation of ammonia in the blood.
### Signs and Symptoms:
- **Lethargy:** Newborns may appear unusually tired or inactive.
- **Poor feeding:** Difficulty in feeding and poor weight gain.
- **Vomiting:** Frequent episodes of vomiting, especially in newborns.
- **Seizures:** Occurrence of seizures due to high ammonia levels.
- **Irritability:** Increased fussiness or irritability.
- **Coma:** Severe cases can lead to coma and potentially death if untreated.
- **Developmental delay:** Delays in reaching developmental milestones.
- **Intellectual disability:** Long-term cognitive impairment in older children or adults.
The presentation and severity of symptoms can vary based on the residual activity of the enzyme. - Prognosis
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Argininosuccinate synthetase deficiency, also known as citrullinemia type I, is a urea cycle disorder. The prognosis can vary significantly depending on the severity of the condition and how early it is diagnosed and treated. Early intervention and ongoing management are crucial.
With appropriate medical treatment, which typically includes dietary restrictions and medications to manage ammonia levels, individuals with this condition can live relatively normal lives. However, in severe cases, especially if diagnosis and treatment are delayed, there may be significant neurological impairment or even life-threatening complications. Liver transplantation may also be considered in some severe cases.
Newborns with severe forms of the disorder may present with symptoms shortly after birth, and without immediate treatment, the condition can lead to catastrophic neurological damage or death. Milder forms may present later in life and generally have a better long-term outlook with proper management. - Onset
- Argininosuccinate synthetase deficiency, also known as citrullinemia type I, typically presents in newborns within the first few days of life. Symptoms can include lethargy, vomiting, seizures, and poor feeding due to hyperammonemia.
- Prevalence
- Prevalence data for argininosuccinate synthetase deficiency (also known as citrullinemia type I) is relatively scarce due to its rarity. However, it's estimated to affect approximately 1 in 57,000 to 250,000 live births worldwide. Occurrence rates can vary significantly by population and region.
- Epidemiology
- Argininosuccinate synthetase deficiency, also known as citrullinemia type I, is a rare autosomal recessive disorder. The epidemiology data indicates an estimated prevalence of 1 in 57,000 to 1 in 250,000 live births worldwide. It is more commonly identified in individuals of East Asian descent, particularly in Japan, where the incidence is slightly higher. Due to its rarity, specific epidemiologic data can be variable and may depend on regional genetic screenings and diagnostic capabilities.
- Intractability
- Argininosuccinate synthetase deficiency, also known as citrullinemia type I, can be challenging to manage but is not inherently intractable. This metabolic disorder, part of the urea cycle disorders, requires lifelong management including dietary restrictions, supplements, and sometimes medications to help remove excess ammonia from the bloodstream. Some cases may require liver transplantation to achieve a long-term solution. While the condition is serious and requires diligent care, with proper management, many individuals can lead a relatively normal life.
- Disease Severity
- Disease severity for argininosuccinate synthetase deficiency, also known as citrullinemia type I, can vary widely. It ranges from mild forms with few symptoms to severe forms that can be life-threatening, particularly in neonates. Symptoms may include lethargy, vomiting, seizures, and coma due to hyperammonemia. Prompt diagnosis and treatment are crucial for managing the condition.
- Healthcare Professionals
- Disease Ontology ID - DOID:9273
- Pathophysiology
- Argininosuccinate synthetase deficiency, also known as citrullinemia type I, is a urea cycle disorder caused by a deficiency in the enzyme argininosuccinate synthetase. This enzyme is crucial for converting citrulline and aspartate into argininosuccinate in the urea cycle, which helps in the removal of excess nitrogen from the body. Due to the enzyme deficiency, ammonia and other toxic substances accumulate in the blood, leading to hyperammonemia. This can result in severe neurological symptoms, including lethargy, vomiting, seizures, and, if untreated, can lead to coma and potentially death.
- Carrier Status
- Carrier status for argininosuccinate synthetase deficiency, also known as citrullinemia type I, refers to individuals who have one mutated copy of the ASS1 gene and one normal copy. These carriers typically do not exhibit symptoms of the disorder but can pass the mutated gene to their offspring, who may be affected if they inherit two mutated copies.
- Mechanism
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Argininosuccinate synthetase deficiency, also known as citrullinemia type I (CTLN1), is a genetic disorder that primarily affects the urea cycle, a series of chemical reactions that takes place in the liver to remove ammonia from the bloodstream.
**Mechanism:**
The deficiency is caused by mutations in the ASS1 gene, which encodes argininosuccinate synthetase, an enzyme crucial for the urea cycle. This enzyme catalyzes the conversion of citrulline and aspartate to argininosuccinate. When the enzyme is deficient or non-functional, the urea cycle is disrupted, leading to the accumulation of toxic levels of ammonia in the blood—a condition known as hyperammonemia.
**Molecular Mechanisms:**
1. **Gene Mutations:** Mutations in the ASS1 gene result in either reduced activity or complete inactivity of the argininosuccinate synthetase enzyme.
2. **Impaired Enzyme Function:** These mutations can lead to structural changes in the enzyme, preventing it from binding to its substrates or catalyzing the reaction efficiently.
3. **Ammonia Accumulation:** The impaired urea cycle fails to convert ammonia into urea for excretion. Elevated ammonia levels are neurotoxic and can cause neurological symptoms.
4. **Secondary Metabolite Accumulation:** Citrulline and other precursors accumulate in the blood and urine because they cannot be processed further in the cycle.
Patients with this condition typically present with symptoms in newborns or early infancy, including lethargy, poor feeding, vomiting, and, in severe cases, seizures and coma due to hyperammonemia. Early diagnosis and management, including dietary restrictions and medications to reduce ammonia levels, are crucial for preventing severe outcomes. - Treatment
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There are multiple treatment methods. Low protein diets are intended to minimize production of ammonia. Arginine, sodium benzoate and sodium phenylacetate help to remove ammonia from the blood. Dialysis may be used to remove ammonia from the blood when it reaches critical levels.
In some cases, liver transplant has been successful. - Compassionate Use Treatment
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Argininosuccinate synthetase deficiency, also known as citrullinemia type I, is a urea cycle disorder that can result in severe hyperammonemia. For compassionate use or experimental treatments, options may include:
1. **Liver Transplantation:** This can potentially cure the metabolic defect by providing a functional enzyme for the urea cycle.
2. **Gene Therapy:** Although still investigational, advancements in gene therapy may offer future treatment possibilities.
3. **Nitrogen Scavenging Agents:** Such as phenylbutyrate or glycerol phenylbutyrate are often used off-label to help reduce ammonia levels.
4. **Sodium Benzoate:** Another agent to help reduce ammonia levels that may be used in off-label treatment protocols.
5. **Experimental Drugs:** Clinical trials may be available offering access to new and experimental treatments.
Consultation with a metabolic specialist is essential for the latest information and treatment options. - Lifestyle Recommendations
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For individuals with argininosuccinate synthetase deficiency (also known as citrullinemia type I), here are some general lifestyle recommendations:
1. **Dietary Management**:
- Adopt a low-protein diet to minimize ammonia production.
- Use specialized medical formulas that provide necessary nutrients without excess nitrogen.
- Regularly consult with a dietitian specialized in metabolic disorders.
2. **Medication**:
- Take prescribed medications such as sodium benzoate, sodium phenylbutyrate, or arginine supplements to help manage ammonia levels.
3. **Regular Monitoring**:
- Frequent blood tests to monitor ammonia and amino acid levels.
- Regular check-ups with a metabolic specialist.
4. **Emergency Plan**:
- Have an emergency protocol in place for hyperammonemia crises, which might include immediate medical attention and hospitalization.
5. **Avoid Triggers**:
- Avoid situations that could lead to increased nitrogen in the body, such as fasting, dehydration, or infections.
6. **Supportive Therapies**:
- Engage in therapies to address developmental delays or neurological issues if they arise.
It's important to tailor these recommendations based on individual needs and under the guidance of healthcare professionals. - Medication
- Argininosuccinate synthetase deficiency, also known as Citrullinemia Type I, is typically managed through dietary modifications and medications to reduce ammonia levels in the blood. Medications commonly used include sodium phenylbutyrate, sodium benzoate, and arginine supplements. These drugs help to facilitate the removal of excess nitrogen from the body. Additionally, patients might benefit from specialized amino acid formulas with reduced protein content. Regular monitoring and medical supervision are crucial.
- Repurposable Drugs
- Argininosuccinate synthetase deficiency, a urea cycle disorder, commonly requires specific treatments that manage ammonia levels, such as sodium phenylbutyrate and sodium benzoate. Research into repurposable drugs for this condition is ongoing. Always consult a healthcare professional for the most current treatment options.
- Metabolites
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Argininosuccinate synthetase deficiency is a urea cycle disorder characterized by an impaired ability to remove ammonia from the blood. Key metabolites involved include:
1. Elevated ammonia levels (hyperammonemia)
2. Elevated citrulline levels
3. Decreased arginine levels
4. Elevated orotic acid levels
These metabolite imbalances result from the defective enzyme argininosuccinate synthetase, which disrupts the conversion of citrulline and aspartate into argininosuccinate, leading to the accumulation and depletion of specific metabolites. - Nutraceuticals
- Argininosuccinate synthetase deficiency, also known as classic citrullinemia, is a urea cycle disorder that leads to an accumulation of ammonia in the blood. Nutraceuticals are not a primary treatment for this condition; however, dietary management is crucial. This typically includes a low-protein diet and the use of special amino acid formulas that limit ammonia production. Ammonia-scavenging drugs like sodium phenylbutyrate or glycerol phenylbutyrate may also be used. Nanotechnology applications are still largely experimental and not yet a standard treatment approach for this disorder.
- Peptides
- Argininosuccinate synthetase deficiency, also known as citrullinemia type I, is a genetic disorder that disrupts the urea cycle, leading to ammonia accumulation in the blood. It is autosomal recessive and caused by mutations in the ASS1 gene, which encodes the enzyme argininosuccinate synthetase. This enzyme catalyzes the conversion of citrulline and aspartate into argininosuccinate. The absence or malfunction of this enzyme results in toxic levels of ammonia, potentially leading to severe neurological damage and other complications. Treatment often involves dietary management and medications to reduce ammonia levels. Peptides and nanotechnology are areas of ongoing research but are not standard treatments for this condition currently.