Carbamoyl Phosphate Synthetase Deficiency
Disease Details
Family Health Simplified
- Description
- Carbamoyl phosphate synthetase deficiency is an autosomal recessive urea cycle disorder where the enzyme CPS1 is deficient, leading to an accumulation of ammonia in the blood.
- Type
- Carbamoyl phosphate synthetase deficiency is a metabolic disorder that affects the urea cycle. The type of genetic transmission for this disorder is autosomal recessive.
- Signs And Symptoms
-
Carbamoyl phosphate synthetase deficiency is a rare genetic disorder affecting the urea cycle.
Signs and symptoms include:
1. Hyperammonemia: This can lead to symptoms such as lethargy, vomiting, and poor feeding in infants.
2. Neurological symptoms: Irritability, seizures, developmental delay, and intellectual disability.
3. Hypotonia: Reduced muscle tone.
4. Respiratory alkalosis: Elevated blood pH due to rapid breathing.
5. Coma: In severe cases, untreated hyperammonemia can lead to coma and death.
Early diagnosis and treatment are crucial to manage symptoms and improve outcomes. - Prognosis
-
Carbamoyl phosphate synthetase deficiency (CPS1 deficiency) is a rare genetic disorder that affects the urea cycle, leading to an inability to properly dispose of ammonia in the body. The prognosis of CPS1 deficiency varies widely depending on the severity of the condition and the effectiveness of medical management.
In severe cases, the prognosis can be poor without early diagnosis and aggressive treatment. Infants with severe forms typically present with hyperammonemia (elevated ammonia levels) shortly after birth, which can lead to neurological damage, coma, or even death if not promptly treated.
With early detection, aggressive management, and strict adherence to dietary and medical protocols, individuals with milder forms of CPS1 deficiency can lead relatively normal lives, although they may still experience metabolic crises. Long-term outcomes improve significantly with ongoing medical care and monitoring to prevent hyperammonemia.
The prognosis also depends on the presence of any associated complications or coexisting conditions, as well as the individual's response to treatments, such as dietary modifications, medications, and potentially liver transplantation in severe cases. Regular follow-up with a metabolic specialist is crucial for optimizing the prognosis. - Onset
- The onset of carbamoyl phosphate synthetase deficiency typically occurs in the neonatal period, usually within the first few days of life, although a milder, late-onset form can manifest in childhood or even adulthood.
- Prevalence
- Carbamoyl phosphate synthetase I (CPSI) deficiency is a rare genetic disorder. Although exact prevalence data are not well established due to its rarity, it is estimated to affect roughly 1 in 200,000 to 1 in 800,000 individuals worldwide.
- Epidemiology
- Carbamoyl phosphate synthetase I (CPSI) deficiency is a rare genetic disorder. It is an inherited metabolic disorder that is part of a group of diseases known as urea cycle disorders. The prevalence of CPSI deficiency is estimated to be approximately 1 in 800,000 to 1 in 1,300,000 live births. This disorder has no particular ethnic or geographical predilection and can affect individuals of any background.
- Intractability
- Carbamoyl phosphate synthetase I deficiency (CPS1 deficiency) is a rare genetic disorder that can be challenging to manage. It is characterized by an inability to properly process nitrogen, leading to elevated levels of ammonia in the blood, which is toxic. The condition requires prompt and ongoing intervention to manage symptoms and prevent complications. While it is not curable, it can be managed with a combination of dietary restrictions, medications, and in some cases, liver transplantation. Therefore, CPS1 deficiency is not entirely intractable but does present significant management challenges.
- Disease Severity
- Carbamoyl phosphate synthetase (CPS) deficiency is a severe metabolic disorder. It falls under the category of urea cycle disorders, where the body's ability to remove waste nitrogen is impaired. Symptoms often begin in the neonatal period and can include lethargy, vomiting, seizures, and coma due to hyperammonemia. If left untreated, CPS deficiency can lead to significant neurological damage and is potentially life-threatening. Early diagnosis and management are crucial to improve outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:9280
- Pathophysiology
- Mutations in SLC25A15 cause ornithine translocase deficiency. Ornithine translocase deficiency belongs to a class of metabolic disorders referred to as urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. The SLC25A15 gene provides instructions for making a protein called a mitochondrial ornithine transporter. This protein is needed to move a molecule called ornithine within the mitochondria (the energy-producing centers in cells). Specifically, this protein transports ornithine across the inner membrane of mitochondria to the region called the mitochondrial matrix, where it participates in the urea cycle. Mutations in the SLC25A15 gene result in a mitochondrial ornithine transporter that is unstable or the wrong shape, and which cannot bring ornithine to the mitochondrial matrix. This failure of ornithine transport causes an interruption of the urea cycle and the accumulation of ammonia, resulting in the signs and symptoms of ornithine translocase deficiency.This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene
- Carrier Status
-
Carrier status for carbamoyl phosphate synthetase deficiency typically follows an autosomal recessive inheritance pattern. This means that carriers have one normal allele and one mutated allele but usually do not exhibit symptoms of the disorder. Carriers can pass the mutated gene to their offspring, who may develop the condition if they inherit the mutated gene from both parents.
The term "nan" seems unclear in this context. If you intended to ask about something specific regarding "nan", please provide more details for clarity. - Mechanism
-
Carbamoyl phosphate synthetase I deficiency (CPS1 deficiency) is a rare inherited disorder that affects the urea cycle, which is responsible for removing ammonia from the body.
**Mechanism:**
- CPS1 deficiency is caused by mutations in the CPS1 gene, which encodes the enzyme carbamoyl phosphate synthetase I. This enzyme is located in the liver mitochondria and plays a critical role in the first step of the urea cycle.
- The primary function of CPS1 is to convert ammonia and bicarbonate into carbamoyl phosphate, which then enters the urea cycle for further processing and eventual excretion of ammonia as urea.
**Molecular Mechanisms:**
- Mutations in the CPS1 gene can lead to reduced activity or complete inactivity of the CPS1 enzyme. This results in the accumulation of ammonia in the bloodstream, a condition known as hyperammonemia.
- Hyperammonemia can cause toxic effects on the central nervous system, leading to symptoms such as lethargy, vomiting, seizures, and, in severe cases, coma.
- The molecular mechanisms behind the deficiency often involve missense mutations, nonsense mutations, deletions, or insertions within the CPS1 gene. These genetic alterations can disrupt the enzyme's active site, stability, or overall conformation, leading to impaired or absent enzymatic function.
- The reduced formation of carbamoyl phosphate impairs the urea cycle, preventing the effective detoxification of ammonia derived from protein metabolism.
Early diagnosis and management are crucial to mitigate the effects of CPS1 deficiency, and treatment may involve dietary modifications, supplements to bypass the metabolic block, and in some cases, liver transplantation. - Treatment
- Treatments include discontinuation of protein intake, intravenous infusion of glucose and, as needed, infusion of supplemental arginine and the ammonia removal drugs, sodium phenylacetate and sodium benzoate.
- Compassionate Use Treatment
-
Carbamoyl phosphate synthetase I (CPS1) deficiency is a rare urea cycle disorder that typically requires specialized medical management. Compassionate use and experimental treatments are often necessary due to the severity and rarity of the disorder. Possible compassionate use and experimental treatments include:
1. **Carglumic Acid**: Though mainly approved for treating N-acetylglutamate synthase (NAGS) deficiency, carglumic acid has been used off-label to manage hyperammonemia in CPS1 deficiency.
2. **Ammonia Scavengers**: Drugs like sodium phenylbutyrate, sodium benzoate, and sodium phenylacetate can be used to help reduce ammonia levels in the blood. While not a cure, they are critical in managing acute hyperammonemia episodes.
3. **Liver Transplantation**: In severe cases, liver transplantation can provide a potential cure by replacing the deficient enzyme, though this is a major procedure with significant risks and long-term implications.
4. **Gene Therapy**: Experimental gene therapy approaches are being researched to address enzyme deficiencies at the genetic level, though this is still in early stages for CPS1 deficiency.
5. **Dichloroacetate (DCA)**: This compound has been tested experimentally to see if it can help manage some metabolic aspects of urea cycle disorders.
These treatments are often pursued under the guidance of a medical professional specializing in metabolic disorders due to the complexity and risks involved. - Lifestyle Recommendations
-
For individuals with carbamoyl phosphate synthetase deficiency (CPS1 deficiency), specific lifestyle recommendations include:
1. **Dietary Management**:
- Adopt a low-protein diet to reduce the amount of ammonia produced from protein metabolism.
- Utilize special medical formulas and foods that are tailored for metabolic disorders to ensure adequate nutrition while controlling ammonia levels.
2. **Frequent Monitoring**:
- Regular blood tests to monitor ammonia levels and other metabolic parameters.
- Monitor dietary intake meticulously to adjust protein levels as necessary based on metabolic control and growth needs.
3. **Medication Adherence**:
- Use medications as prescribed, such as ammonia-scavenging drugs (e.g., sodium phenylbutyrate or sodium benzoate), to help manage ammonia levels.
4. **Emergency Protocols**:
- Have an emergency plan in place, including specific instructions for managing hyperammonemia (high ammonia levels).
- Keep contact information for metabolic specialists easily accessible.
5. **Avoid Strenuous Activities**:
- Limit or modify physical activities that may exacerbate metabolic stress, especially activities resulting in muscle breakdown and increased ammonia production.
6. **Regular Follow-Up**:
- Schedule regular follow-up appointments with metabolic and genetic specialists to monitor the disease progression and adjust treatment plans as needed.
7. **Education and Support**:
- Educate family members and caregivers about the condition, dietary needs, and emergency protocols.
- Consider support groups or counseling for emotional and psychological support.
These recommendations are aimed at maintaining metabolic stability and preventing complications associated with elevated ammonia levels. - Medication
-
Carbamoyl phosphate synthetase I deficiency is a rare urea cycle disorder. Management often includes medications and nutritional interventions to reduce ammonia levels and prevent hyperammonemia. Common medications include:
- **Ammonia scavengers**: Sodium phenylbutyrate or glycerol phenylbutyrate, which help to remove excess nitrogen.
- **Arginine or citrulline supplements**: To help support the urea cycle and reduce ammonia levels.
These medications are typically used in conjunction with a low-protein diet and close monitoring of plasma ammonia levels. - Repurposable Drugs
- Carbamoyl phosphate synthetase deficiency (CPS1 deficiency) is a rare urea cycle disorder. There are currently no widely accepted repurposable drugs specifically for CPS1 deficiency. The mainstay of treatment typically involves dietary protein restriction, supplementation with essential amino acids, and the use of medications to help remove excess ammonia from the body, such as sodium benzoate and sodium phenylbutyrate. Experimental treatments and gene therapy may offer potential future options. Always consult with a specialist to explore the latest treatment approaches.
- Metabolites
- The primary metabolite of concern in carbamoyl phosphate synthetase deficiency is ammonia. Due to the enzyme deficiency, the urea cycle is disrupted, leading to the accumulation of ammonia in the blood, which can be toxic. Other metabolites that may be affected include citrulline and orotic acid (decreased levels). Elevated levels of glutamine may also be observed.
- Nutraceuticals
- Carbamoyl phosphate synthetase deficiency is a rare urea cycle disorder that impairs the body's ability to detoxify ammonia. Nutraceutical management approaches are not typically standard treatment, but patients may benefit from dietary modifications, particularly low-protein diets to reduce ammonia production. However, it's crucial for patients to be under the care of a metabolic specialist. Conventional treatments include medications such as sodium benzoate or phenylbutyrate that help remove excess ammonia from the bloodstream. Proper consultation with healthcare providers is essential for personalized care.
- Peptides
- Carbamoyl phosphate synthetase deficiency is a rare metabolic disorder that primarily affects the urea cycle, leading to the inability to convert ammonia to urea. While "peptides, nan" is not clear in this context, it is possible that you are inquiring about specific aspects of treatment or research connected to peptides at a nanoscale level. Current treatment includes dietary management to limit ammonia production, medications like sodium phenylbutyrate, and sometimes liver transplantation. There is ongoing research in gene therapy and enzyme replacement that might use novel delivery mechanisms, potentially including nanoscale peptides, but such treatments are not standard as of now.