Ornithine Transcarbamylase Deficiency (OTC Deficiency) is an X-chromosome linked urea cycle disorder resulting from defects in the OTC gene. Like all other urea cycle disorders, OTC deficiency also usually becomes evident in the first few days of an affected neonate's life, and is characterized by severe lethargy, loss of appetite, seizures, lack of control on breathing rate or body temperature, liver damage, mood swings, and irrational behavior. In a minority of cases, the symptoms and features of the condition appear much later in life. Since this is an X-linked recessive condition, males are more likely to be affected than females. However, interestingly, some women who are carriers for the defective gene have been shown to develop the condition later in life. In most such cases, this is precipitated by anorexia, malnutrition, or some form of trauma. It was estimated that 1 in every 80,000 births is affected with OTC deficiency. However, a much more recent update has put this estimate up at 1:20,000 live births, making it one of the most common of the urea cycle disorders.
Interestingly, males with OTC deficiency have been shown to be sensitive to valproate, an anti-convulsant; valproate administration causing acute liver failure in these patients.
Diagnosis is based upon the two cardinal features of hyperammonemia and elevated urinary orotic acid level. Serum ornithine, glutamine, and alanine levels may be reduced. Assay of enzymatic activity of OTC provides confirmation of the diagnosis. Genetic testing, both post- and ante-natal, is also available. Management is similar to that of other urea cycle disorders, and includes dialysis, managing diet with a high calorie-low protein intake, administering arginine chloride and cardiac pressors, and lowering the nitrogen level in the blood.