Summary about Disease
Carbamoyl phosphate synthetase I deficiency (CPS1 deficiency) is a rare genetic metabolic disorder that causes a buildup of ammonia in the blood (hyperammonemia). CPS1 is an enzyme that is essential for the urea cycle, which removes ammonia from the body. Without enough functional CPS1 enzyme, ammonia accumulates to toxic levels, primarily affecting the brain and other organs. It is classified as a urea cycle disorder.
Symptoms
Symptoms can vary in severity and age of onset. They may include:
Lethargy
Poor feeding (in infants)
Vomiting
Irritability
Seizures
Coma
Developmental delay (in later onset cases)
Intellectual disability (if left untreated)
Ataxia (lack of muscle coordination)
Hyperventilation
Respiratory distress
Causes
CPS1 deficiency is caused by mutations in the CPS1 gene. This gene provides instructions for making the carbamoyl phosphate synthetase I enzyme. The deficiency is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
4. Medicine used Treatment focuses on lowering ammonia levels. Medications may include:
Sodium benzoate and sodium phenylacetate/phenylbutyrate: These drugs provide alternative pathways for ammonia removal.
L-arginine or L-citrulline: These amino acids can help stimulate the urea cycle.
N-carbamylglutamate (Carbaglu): This drug is a CPS1 activator and can be helpful in some patients.
Ammonia Detoxicants: Medications specifically designed to lower blood ammonia levels during acute hyperammonemic crises.
Liver Transplant: In severe cases, a liver transplant may be considered as a curative option.
Is Communicable
No, CPS1 deficiency is not communicable. It is a genetic disorder, not an infectious disease.
Precautions
Precautions focus on managing ammonia levels:
Dietary management: A low-protein diet is crucial to limit ammonia production.
Regular monitoring: Blood ammonia levels need to be monitored frequently, especially during illness or stress.
Avoid prolonged fasting: Fasting can trigger hyperammonemia.
Prompt treatment of illness: Even minor illnesses can exacerbate hyperammonemia.
Genetic counseling: For families with a history of CPS1 deficiency, genetic counseling is recommended.
How long does an outbreak last?
CPS1 deficiency does not have "outbreaks" in the traditional sense. Hyperammonemic crises can occur at any time, especially during illness or periods of stress. The duration of a hyperammonemic crisis varies depending on the severity and how quickly it is treated. Prompt treatment is essential to minimize neurological damage. The effects of the illness or crisis, however, can have lifelong impacts, like cognitive impairment and development delays.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many states include CPS1 deficiency in their newborn screening programs.
Blood tests: Elevated ammonia levels, especially after feeding, are suggestive.
Urine tests: Measuring orotic acid levels can help differentiate CPS1 deficiency from other urea cycle disorders.
Genetic testing: Confirms the diagnosis by identifying mutations in the CPS1 gene.
Liver biopsy: In some cases, a liver biopsy may be performed to measure CPS1 enzyme activity.
Timeline of Symptoms
9. Timeline of symptoms
Neonatal onset: Symptoms appear within the first few days of life.
Late onset: Symptoms can appear later in infancy or childhood, often triggered by illness or stress. The progression and severity of symptoms will vary depending on the individual.
Important Considerations
Early diagnosis and treatment are crucial to prevent neurological damage.
Lifelong management is required, including dietary restrictions, medications, and regular monitoring.
Patients and families require ongoing support from metabolic specialists, dietitians, and genetic counselors.
Emergency treatment protocols should be in place to manage hyperammonemic crises.
Liver transplantation can be considered for severe cases.