Summary about Disease
Argininosuccinate synthetase deficiency (ASS deficiency), also known as citrullinemia type I, is a rare inherited metabolic disorder that disrupts the urea cycle. The urea cycle is a sequence of biochemical reactions that occur in the liver that process nitrogen, a waste product of protein metabolism, into urea, which is then excreted in urine. In ASS deficiency, a defect in the argininosuccinate synthetase enzyme prevents the proper conversion of citrulline to argininosuccinic acid, leading to an accumulation of ammonia (hyperammonemia) and other toxic substances in the blood. This can cause neurological damage and other serious health problems. There are different forms of the disease, with varying degrees of severity.
Symptoms
Symptoms vary based on the severity of the deficiency.
Neonatal-onset (Severe):
Lethargy/Poor Feeding
Vomiting
Irritability
Seizures
Coma
Respiratory distress
Late-onset (Milder):
Headaches
Protein avoidance
Irritability
Developmental delay
Learning disabilities
Hyperactivity
Episodic hyperammonemia triggered by illness or stress.
Causes
ASS deficiency is caused by mutations in the ASS1 gene. This gene provides instructions for making the argininosuccinate synthetase enzyme. The mutations reduce or eliminate the function of the enzyme, disrupting the urea cycle. 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 lowering ammonia levels and preventing future build-up.
Sodium Benzoate and Sodium Phenylacetate/Phenylbutyrate: These medications help the body eliminate nitrogenous waste by providing alternative pathways for excretion.
Arginine Supplementation: Helps to promote the urea cycle when argininosuccinate synthetase activity is reduced.
Ammonium Detoxicants: Medications like glycerol phenylbutyrate are also used to reduce ammonia.
Liver Transplant: In severe cases, a liver transplant may be considered as a curative option.
Is Communicable
No, ASS deficiency is not communicable. It is a genetic disorder caused by a gene mutation and cannot be spread from person to person.
Precautions
Dietary Management: A low-protein diet is essential to reduce the production of ammonia. Work with a registered dietitian to create a safe and appropriate meal plan.
Avoid Prolonged Fasting: Fasting can trigger hyperammonemia.
Monitor Ammonia Levels: Regular monitoring is crucial to detect and treat hyperammonemic episodes promptly.
Prompt Medical Attention: Seek immediate medical attention if symptoms of hyperammonemia develop (e.g., vomiting, lethargy, seizures).
Genetic Counseling: Families with a history of ASS deficiency should consider genetic counseling to understand the risk of recurrence.
How long does an outbreak last?
Outbreak" is not the correct term here, as this is not an infectious disease. Episodes of hyperammonemia can last from several hours to several days, depending on the severity and promptness of treatment. Chronic symptoms persist throughout life.
How is it diagnosed?
Newborn Screening: Some states include citrullinemia in their newborn screening programs, which involves testing a blood sample for elevated citrulline levels.
Blood Tests: High ammonia and citrulline levels in the blood are suggestive of ASS deficiency.
Urine Tests: Elevated levels of orotic acid can also be present.
Genetic Testing: Confirms the diagnosis by identifying mutations in the ASS1 gene.
Enzyme Assay: Measures the activity of the argininosuccinate synthetase enzyme in liver tissue.
Timeline of Symptoms
Neonatal-onset: Symptoms typically appear within the first few days of life.
Late-onset: Symptoms can appear any time from infancy through adulthood. They are often triggered by illness, stress, or high protein intake. The timeline can be very variable in later-onset cases.
Important Considerations
Early Diagnosis and Treatment: Crucial to prevent neurological damage and improve long-term outcomes.
Lifelong Management: Requires ongoing dietary management, medication, and monitoring.
Emergency Protocol: Families and caregivers should have a clear emergency protocol for managing hyperammonemic crises.
Multidisciplinary Care: Management requires a team of specialists including a metabolic specialist, geneticist, dietitian, and neurologist.
Support Groups: Connecting with other families affected by urea cycle disorders can provide valuable support and information.