Summary about Disease
Citrullinemia is a rare, inherited metabolic disorder that causes ammonia to accumulate in the blood. Ammonia is a toxic substance that is produced when the body breaks down proteins. Normally, the body processes ammonia through the urea cycle, a series of chemical reactions that occur in the liver. Citrullinemia occurs when one of the enzymes in the urea cycle, argininosuccinate synthetase (ASS), is deficient. This deficiency prevents the urea cycle from functioning properly, leading to a buildup of ammonia. There are two main types: Type I (classic citrullinemia) and Type II. Type I is more common and usually presents in newborns. Type II is less common and typically presents later in life.
Symptoms
Newborns (Type I): Poor feeding, vomiting, lethargy, irritability, seizures, hypotonia (decreased muscle tone), respiratory distress, and coma.
Late-onset (Type II): Confusion, disorientation, tremors, slurred speech, seizures, behavioral changes, nausea, vomiting, abdominal pain, and aversion to protein-rich foods. Some adults may be asymptomatic until triggered by illness, stress, or high protein intake.
Causes
Citrullinemia is caused by mutations in the ASS1 gene (for Type I) or the *SLC25A13* gene (for Type II). These genes provide instructions for making the argininosuccinate synthetase enzyme (Type I) or a liver mitochondrial aspartate glutamate carrier protein (citrin, Type II), which are vital for the urea cycle function. The disorder 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 lowering ammonia levels in the blood. Medications include:
Sodium benzoate and sodium phenylacetate/phenylbutyrate: These medications help to remove ammonia from the body by providing alternative pathways for nitrogen excretion.
L-arginine: Supplementation with arginine can help stimulate the urea cycle in some cases of Type I citrullinemia.
Ammonium scavengers: These medications help to bind to ammonia and remove it from the body.
Liver transplantation: In severe cases, a liver transplant may be necessary to restore proper urea cycle function.
Is Communicable
No, citrullinemia is not communicable. It is a genetic disorder and cannot be spread from person to person.
Precautions
Dietary management: A low-protein diet is crucial to reduce ammonia production. Careful monitoring of protein intake is necessary.
Regular monitoring: Frequent blood tests to monitor ammonia levels are essential.
Avoidance of triggers: Individuals with late-onset citrullinemia should avoid triggers such as high-protein diets, alcohol consumption, and certain medications.
Genetic counseling: Families with a history of citrullinemia should consider genetic counseling to assess their risk of having affected children.
Emergency preparedness: Patients and their families should be educated on the signs of a hyperammonemic crisis and have a plan in place for emergency treatment.
How long does an outbreak last?
Citrullinemia is not an "outbreak" situation. Rather, it is a chronic condition with the potential for acute episodes of hyperammonemia (high ammonia levels in the blood). The duration of a hyperammonemic crisis can vary widely depending on the severity of the condition, the promptness of diagnosis and treatment, and the individual's response to therapy. Without prompt intervention, a hyperammonemic crisis can be life-threatening. With appropriate treatment, ammonia levels can be brought under control within days to weeks.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many states include citrullinemia in their newborn screening programs, which involves testing a small blood sample for elevated citrulline levels.
Blood tests: Elevated levels of citrulline in the blood are a hallmark of citrullinemia. Ammonia levels are also usually elevated.
Urine tests: Analysis of urine can help identify other metabolic abnormalities.
Genetic testing: Genetic testing can confirm the diagnosis by identifying mutations in the ASS1 or *SLC25A13* genes.
Liver biopsy: In some cases, a liver biopsy may be performed to assess enzyme activity.
Timeline of Symptoms
Type I (Newborn): Symptoms typically appear within the first few days of life (24-72 hours).
Type II (Late-onset): Symptoms can appear at any time from childhood to adulthood. The onset can be triggered by illness, stress, or dietary changes. The timeline can vary significantly depending on the individual.
Important Considerations
Early diagnosis and treatment are crucial to prevent severe neurological damage and death.
Long-term management requires a multidisciplinary approach, including a metabolic specialist, dietitian, and genetic counselor.
Adherence to dietary restrictions and medication regimens is essential for controlling ammonia levels.
Liver transplantation can be a life-saving option for individuals with severe citrullinemia.
Individuals with citrullinemia should be monitored throughout their lives for potential complications.