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.
In a retrospective analysis of IEMs diagnosed over a 12-year period (1998-2010) in a hospital in Lebanon, Karam et al. (2013) found 24 patients diagnosed with ornithine transcarbamylase deficiency. The median age of diagnosis was 13-years.
Joshi et al. (2002) carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between June 1998 and December 2000. Among 82 patients, only one was diagnosed with OTC deficiency [CTGA Database Editor's note: Computed annual incidence rate is 0.8/100,000].
Al-Riyami et al. (2012) reported on the types and patterns of IEMs encountered in a sample of 1100 high-risk neonates referred to SQU Hospital in Oman over a 10-year period (1998-2002). MS/MS was used to analyze blood samples from heel pricks. A total of 119 of these neonates were found to test positive for an IEM. OTC Deficiency was detected in two male neonates from different families. One of the patients had a family history of the condition. Consangunity was reported in one of the families.