Argininosuccinic aciduria is classified as a urea cycle disorder resulting from the deficiency of the enzyme argininosuccinate lyase.
Argininosuccinic aciduria leads to elevated levels of argininosuccinic acid and citrulline in the body. Consequently, there is a potential buildup of ammonia in the body, contributing to disease symptoms. The severe form is evident within the first few days of life, with symptoms such as vomiting, lethargy, hypothermia, poor feeding, and rapid breathing (tachypnea). If left untreated, symptoms worsen, leading to seizures, coma, and death. Early symptoms may also include brittle hair and an enlarged liver. There is a late-onset form that presents with a broad range of symptoms, including periodic increases in ammonia levels, developmental delay or intellectual disability, and behavioral abnormalities, among others.
There is no cure for argininosuccinic aciduria and the prognosis depends upon the severity of the symptoms. Treatments to reduce ammonia levels in the body are available but do not prevent many of the symptoms including cognitive issues.
This condition is caused by pathogenic (disease-causing) variants in the ASL gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition.
Other names for this condition are argininosuccinate lyase deficiency, argininosuccinic academia, argininosuccinicaciduria, argininosuccinyl-CoA lyase deficient, arginosuccinase deficiency, and ASL deficiency.