Citrullinemia Type 1 usually becomes evident in the first few days of life. Affected infants typically appear normal at birth, but as ammonia builds up in the body they experience a progressive lack of energy (lethargy), poor feeding, vomiting, seizures, and loss of consciousness. These medical problems are life-threatening in many cases.

Less commonly, a milder form can develop later in childhood or adulthood that is associated with intense headaches, partial loss of vision, problems with balance and muscle coordination (ataxia), and lethargy.