Liver cancer (hepatocellular carcinoma) is described as being associated with OTC deficiency. The risk of developing this malignant liver tumor is probably the highest in patients exhibiting long-term liver damage who have not undergone a transplant. The exact risk, cannot yet be quantified.
Clinically, OTC deficiency can occur either as a severe disease affecting male newborns (it very rarely affects female newborns) or after the newborn period (post-neonatal) in males and females.
Affected children typically appear to be healthy at birth; however, they increasingly lose their sucking behavior when they are two to three days old, resulting in reduced food intake. Affected newborns become increasingly limp and sleepy, and the high level of ammonia in the blood can result in coma. In addition, breathing is accelerated, which can lead to cramping seizures, low body temperature, and severe brain damage.
Even after suffering a coma induced by high blood ammonia levels, the increased risk of an elevated ammonia level remains ever present. Generally, a liver transplant at around 6 months (sometimes earlier) is necessary to prevent further brain damage and increase the quality of life.
In affected males and females with partial OTC deficiency, the disease can manifest for the first time anywhere from infancy to adulthood. It is often the case that initial symptoms, such as intermittent vomiting, consciousness disorders, irritability, failure to thrive, or developmental delays, occur when a change is made from nursing to baby formula or cow’s milk.
In adults with a very mild form of the disease, initial symptoms often manifest after a trigger, such as major injuries, following surgery, after a pregnancy, during cancer therapy, after prolonged fasting, a protein-rich diet, high-dosage cortisone therapy, or an illness associated with fever.
Females who only carry the OTC gene alteration on one of their two X-chromosomes can either present with clear clinical signs or have no obvious symptoms. The extent of symptoms depends on which X-chromosome is inactivated . Around 15% of affected females develop symptoms over the course of their lives.