Citrullinemia, Type 1 (ASS1)

Citrullinemia, type 1 is an autosomal recessive, pan-ethnic disorder caused by pathogenic variants in the gene ASS1. Loss of argininosuccinate synthase 1, encoded by ASS1, results in dysfunction of the urea acid cycle and buildup of excess ammonia in the body. Onset of the classical form occurs within the first few days of life. The clinical presentation includes hyperammonemia, poor feeding, and lethargy which may lead to coma if not treated. Treated children usually develop serious neurological defects. Onset may also occur in adults, where the disease is characterized by periods of hyperammonemia, reduced alertness, headache or migraine. Patients with adult-onset disease may present with liver failure instead of neurological symptoms. Some specific variants have been associated with the development of neonatal or adult-onset disease, although not all phenotypes can be accurately predicted based on genotype.

For information about carrier frequency and residual risk, please see the residual risk table.