argininosuccinic aciduria

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What is Argininosuccinic Aciduria?

Argininosuccinic aciduria (ASL deficiency) is a urea cycle disorder caused by harmful genetic changes (mutations) in the ASL gene. Mutations in ASL cause deficiency of argininosuccinate lyase, which results in the build-up of argininosuccinic acid, citrulline, and toxic ammonia in the body (hyperammonemia). There are two forms of the disease: neonatal-onset form and late-onset form.

Neonatal-Onset Form

The neonatal-onset form is severe. It presents within the first few days of life with symptoms such as vomiting, excessive sleepiness (lethargy), low body temperature (hypothermia), poor feeding, and rapid breathing (tachypnea). Other early symptoms may include brittle hair and an enlarged liver. If left untreated, symptoms will progress and eventually lead to seizures, coma, and death.

Late-Onset Form

The late onset form can have a wide range of symptoms. Symptoms may include developmental delay, intellectual disability, behavioral abnormalities and episodic increases in ammonia levels.

How common is Argininosuccinic Aciduria?

The incidence of argininosuccinic aciduria in the population is 1 in 70,000 births. Argininosuccinic aciduria is more common among individuals of Saudi Arabia and the Druze community.

How is Argininosuccinic Aciduria treated?

Treatment for argininosuccinic aciduria is dietary, through restriction of dietary protein and the taking of arginine supplements. Additionally, medication called nitrogen-scavenging drugs may help maintain lower amounts of ammonia in the body. In individuals whose ammonia levels cannot be managed, or in those with liver cirrhosis, a liver transplant may be considered.

Acute episodes of excess ammonia are treated in a hospital. Though intravenous (IV) supplements and nitrogen-scavenging drugs can help lower the amount of ammonia in the body, filtering the ammonia from the blood directly (hemodialysis) may be necessary if these measures are ineffective.

What is the prognosis for an individual with Argininosuccinic Aciduria?

There is no cure for argininosuccinic aciduria, and the prognosis depends upon the severity of the symptoms. Individuals who have milder symptoms and are provided with early dietary and therapeutic interventions will have a more favorable outcome. However, they will still require long-term management to prevent neurologic and liver damage. Those who have more severe symptoms could experience seizures, coma, and early death. Treatments to reduce ammonia levels in the body do not prevent intellectual disability, liver disease, and brittle hair.