Argininosuccinic aciduria

A rare genetic disorder affecting the urea cycle

Chemical structure of argininosuccinic acid

Argininosuccinic aciduria is a rare genetic disorder that affects the urea cycle, a series of biochemical reactions that occur in the liver to remove ammonia from the bloodstream. This condition is characterized by the accumulation of argininosuccinic acid in the blood and urine, leading to a variety of symptoms and potential complications.

Pathophysiology

Argininosuccinic aciduria is caused by a deficiency of the enzyme argininosuccinate lyase (ASL), which is responsible for the conversion of argininosuccinic acid into arginine and fumarate. This enzyme deficiency disrupts the urea cycle, resulting in the accumulation of ammonia and argininosuccinic acid in the body. Elevated levels of ammonia can be toxic, particularly to the central nervous system, leading to neurological symptoms.

Genetics

The disorder is inherited in an autosomal recessive pattern, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent. The gene responsible for argininosuccinic aciduria is located on chromosome 7 and is known as the ASL gene. Mutations in this gene lead to reduced or absent activity of the argininosuccinate lyase enzyme.

Clinical Presentation

Symptoms of argininosuccinic aciduria can vary widely among affected individuals. Common symptoms include:

• Hyperammonemia
• Vomiting
• Lethargy
• Seizures
• Developmental delay
• Hepatomegaly

In severe cases, the condition can lead to coma and can be life-threatening if not treated promptly.

Diagnosis

Diagnosis of argininosuccinic aciduria is typically made through a combination of clinical evaluation, biochemical testing, and genetic testing. Elevated levels of argininosuccinic acid in the blood and urine are indicative of the disorder. Genetic testing can confirm mutations in the ASL gene.

Treatment

Management of argininosuccinic aciduria involves dietary modifications and medications to reduce ammonia levels. Treatment strategies may include:

• A low-protein diet to reduce ammonia production
• Supplementation with arginine
• Medications such as sodium phenylbutyrate or sodium benzoate to help remove ammonia from the body

In some cases, liver transplantation may be considered as a treatment option.

Prognosis

The prognosis for individuals with argininosuccinic aciduria varies depending on the severity of the condition and the effectiveness of treatment. Early diagnosis and management are crucial for improving outcomes and preventing complications.

Related pages

• Urea cycle disorder
• Hyperammonemia
• Genetic disorder