Summary about Disease
Argininosuccinate lyase deficiency (ASL deficiency), also known as argininosuccinic aciduria, is a rare inherited metabolic disorder that causes the build-up of ammonia and argininosuccinic acid in the blood. It is classified as a urea cycle disorder, which means that the body cannot properly eliminate nitrogen, a waste product of protein metabolism. This leads to hyperammonemia (high levels of ammonia in the blood), which can be toxic to the brain and other organs. The severity of ASL deficiency can vary widely, with some individuals experiencing symptoms shortly after birth (neonatal-onset) and others not developing symptoms until later in life.
Symptoms
Symptoms of ASL deficiency can vary depending on the severity of the condition. Common symptoms include:
Neonatal-onset: Poor feeding, vomiting, lethargy, irritability, seizures, coma, respiratory distress.
Late-onset: Failure to thrive, developmental delays, intellectual disability, behavioral problems, ataxia (lack of coordination), liver enlargement, brittle hair (trichorrhexis nodosa), elevated blood pressure, hyperammonemic episodes triggered by illness or stress.
Causes
ASL deficiency is caused by mutations in the ASL gene. This gene provides instructions for making the argininosuccinate lyase enzyme. This enzyme is responsible for breaking down argininosuccinic acid, an intermediate product in the urea cycle. Mutations in the *ASL* gene lead to a deficiency in this enzyme, which causes argininosuccinic acid and ammonia to accumulate in the blood. ASL deficiency is inherited in an autosomal recessive pattern, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
Treatment for ASL deficiency focuses on lowering ammonia levels in the blood and preventing future build-up. Medications used include:
Ammonia-scavenging drugs: Sodium benzoate, sodium phenylacetate, glycerol phenylbutyrate (Ravicti). These medications help the body eliminate excess nitrogen.
Arginine supplementation: Arginine can help to promote the urea cycle, thus helping to eliminate excess nitrogen.
Lactulose: A synthetic sugar that helps to remove ammonia from the body via stool.
In severe cases: Hemodialysis or hemofiltration may be necessary to rapidly lower ammonia levels.
Is Communicable
No, ASL deficiency is not communicable. It is a genetic disorder caused by a mutation in the ASL gene and is inherited from parents to their offspring. It cannot be spread from person to person through contact or any other means.
Precautions
Precautions for individuals with ASL deficiency and their families include:
Dietary management: Following a low-protein diet to reduce the amount of nitrogen produced in the body. Working with a registered dietitian is essential.
Emergency protocol: Having a plan in place for managing hyperammonemic crises, including knowing when to seek medical attention.
Medication adherence: Taking prescribed medications as directed to help control ammonia levels.
Monitoring: Regular blood tests to monitor ammonia and amino acid levels.
Avoidance of triggers: Identifying and avoiding triggers that can lead to hyperammonemic episodes, such as infections, stress, and prolonged fasting.
Genetic counseling: For families with a history of ASL deficiency, genetic counseling can help to determine the risk of having another affected child.
How long does an outbreak last?
"Outbreak" is not the correct term to use. ASL deficiency is a chronic condition, not an infectious disease. However, individuals with ASL deficiency can experience hyperammonemic episodes, which are periods of elevated ammonia levels in the blood. The duration of a hyperammonemic episode can vary depending on the severity of the episode and the effectiveness of treatment. Prompt and aggressive treatment is essential to resolve hyperammonemia as quickly as possible and prevent long-term complications. Without treatment, hyperammonemia can lead to significant health problems in a relatively short period (days to weeks).
How is it diagnosed?
ASL deficiency is typically diagnosed through a combination of methods:
Newborn screening: Many states include ASL deficiency in their newborn screening programs, which involves testing a small blood sample for elevated levels of argininosuccinic acid.
Blood tests: Elevated levels of ammonia and argininosuccinic acid in the blood can suggest ASL deficiency. Amino acid analysis of plasma/serum and urine is key to diagnosis.
Urine tests: Elevated levels of argininosuccinic acid in the urine can be detected.
Enzyme assay: Measuring the activity of argininosuccinate lyase enzyme in red blood cells or liver tissue.
Genetic testing: Confirming the diagnosis by identifying mutations in the ASL gene.
Timeline of Symptoms
The timeline of symptoms can vary depending on the severity of ASL deficiency:
Neonatal-onset: Symptoms typically appear within the first few days of life (0-7 days).
Late-onset: Symptoms can appear anytime from infancy to adulthood. Delays in development or milestones may be the first indicator, followed by intermittent episodes of hyperammonemia.
Important Considerations
Early diagnosis and treatment: Early diagnosis and prompt treatment are crucial to minimize the risk of brain damage and other complications.
Long-term management: ASL deficiency requires lifelong management, including dietary restrictions, medication, and regular monitoring.
Multidisciplinary care: Optimal care involves a team of healthcare professionals, including a metabolic specialist, geneticist, dietitian, and neurologist.
Family support: Support groups and resources can help families cope with the challenges of living with ASL deficiency.
Liver Transplantation: Liver transplantation can be considered as a treatment option in select individuals with severe disease, especially if medical management is not sufficient.