Summary about Disease
Carbamoyl phosphate synthetase I (CPS1) deficiency is a rare genetic metabolic disorder that disrupts the urea cycle. The urea cycle is a series of biochemical reactions in the liver that removes ammonia, a toxic waste product of protein breakdown, from the blood. CPS1 deficiency is characterized by the inability to produce carbamoyl phosphate, the first step in the urea cycle. This leads to a buildup of ammonia in the blood (hyperammonemia), which can cause severe neurological damage.
Symptoms
Symptoms vary in severity depending on the degree of enzyme deficiency. They can manifest from infancy to adulthood. Common symptoms include:
Lethargy
Poor feeding (in infants)
Vomiting
Irritability
Seizures
Developmental delays
Intellectual disability
Coma
Breathing difficulties
Ataxia (lack of muscle coordination)
Causes
CPS1 deficiency is caused by mutations in the CPS1 gene. This gene provides instructions for making the carbamoyl phosphate synthetase I enzyme. Mutations in this gene lead to a non-functional or deficient enzyme. It is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Treatment focuses on managing hyperammonemia and preventing neurological damage. Common medications include:
Sodium benzoate and sodium phenylacetate/phenylbutyrate: These medications help the body eliminate ammonia by providing alternative pathways for nitrogen excretion.
L-arginine or L-citrulline: Supplementation may help stimulate the urea cycle.
Ammonium scavenging medications: Medications that assist the body in removing ammonia.
Liver transplant: In severe cases, liver transplantation may be considered as a curative option.
Dietary management: A low-protein diet is crucial to reduce ammonia production.
Is Communicable
No, CPS1 deficiency is not communicable. It is a genetic disorder caused by a mutation in the CPS1 gene and cannot be spread from person to person.
Precautions
Precautions focus on preventing hyperammonemic crises:
Strict dietary management: Adhering to a low-protein diet is essential.
Regular monitoring of ammonia levels: Frequent blood tests are needed to monitor ammonia levels and adjust treatment as needed.
Avoidance of triggers: Identify and avoid triggers that can lead to hyperammonemia, such as prolonged fasting, infections, and high-protein meals.
Prompt medical attention: Seek immediate medical attention at the first signs of hyperammonemia (e.g., lethargy, vomiting).
Genetic counseling: For families with a history of CPS1 deficiency, genetic counseling can help assess the risk of having an affected child.
How long does an outbreak last?
CPS1 deficiency is not an "outbreak" type of disease. It's a chronic condition. A hyperammonemic crisis, however, can last from several hours to several days or even weeks, depending on the severity and how quickly it is treated.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many states include CPS1 deficiency in their newborn screening programs. Elevated ammonia levels in the blood can suggest the disorder.
Plasma amino acid analysis: This test can show characteristic amino acid patterns associated with urea cycle defects.
Urine organic acid analysis: This test can help rule out other metabolic disorders.
Enzyme assay: Measuring the activity of CPS1 enzyme in a liver biopsy can confirm the diagnosis.
Genetic testing: Identifying mutations in the CPS1 gene can confirm the diagnosis.
Timeline of Symptoms
Neonatal-onset: Symptoms can appear within the first few days of life.
Late-onset: Symptoms may appear later in infancy, childhood, or even adulthood.
The initial symptoms are often non-specific (e.g., poor feeding, vomiting, lethargy) and progress to more severe neurological symptoms (e.g., seizures, coma) if left untreated.
The timeline and severity of symptoms vary widely depending on the specific mutation and the degree of enzyme deficiency.
Important Considerations
Early diagnosis and treatment are crucial: Prompt intervention can help prevent severe neurological damage and improve long-term outcomes.
Lifelong management is required: Individuals with CPS1 deficiency need lifelong dietary management, medication, and monitoring.
Hyperammonemic crises are medical emergencies: Any signs of hyperammonemia should be treated immediately in a hospital setting.
Family support and education are essential: Families need to be well-informed about the disease and its management.
Liver transplantation: While not a cure for the genetic defect, liver transplantation can correct the metabolic deficiency and improve the patient's quality of life.