FINAL DIAGNOSIS: PARTIAL ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY
Pathophysiology: OTC deficiency is the most common of the urea cycle disorders (UCD).(1).
FINAL DIAGNOSIS: PARTIAL ORNITHINE TRANSCARBAMYLASE (OTC) DEFICIENCY
Pathophysiology: OTC deficiency is the most common of the urea cycle disorders (UCD).(1). The urea cycle converts nitrogen from peripheral (muscle) and dietary sources into urea that is water soluble and can be excreted. Figure 2 (2) is a simplified schematic representation of the urea cycle showing how OTC deficiency leads to the impaired condensation of carbamyl phosphate and ornithine to form citrulline. This impairment leads to reduced ammonia incorporation which, in turn, causes symptomatic hyperammonemia and excess of both substrates for the reaction.
Under normal circumstances urea cycle occurs in hepatic mitochondria. However when excessive carbamyl phosphate it finds its way into the cytosol where it functions as substrate for the carbamoyl phosphate synthetase (CPS) II reaction. This results in orotic acid, which is a normal intermediate in the very tightly regulated pyrimidine biosynthesis. In OTC deficiency neither conversion of CPS to orotate nor hepatic leakage of ornithine can prevent the rapid development of hyperammonemia (1). The accumulation of ammonia and other metabolites causes. cerebral edema.
OTC is encoded for on the OTC gene located on the X chromosome at band Xp21.1. The nature of mutation in the OTC gene is highly variable with more than 150 mutations, most of which are single-base substitutions, having been reported (3). Most mutations are inherited with a significant rate of spontaneous mutation.
Epidemiology: The estimated incidence of 1:80,000 live births may be an underestimation because late onset cases may go undetected. In older individuals, the initial onset can occur at any age up to 40-50 years and beyond. As an X-linked trait, the mutant OTC gene regularly manifests in hemizygous males (1).
Clinical Presentation: Typically the patient is a term newborn who appears well for the first 24 to 48 hours after birth. It becomes symptomatic after feeding has started because human milk or formula provides a protein load. Initial signs include somnolence and poor feeding, usually followed by vomiting, lethargy, and coma central. Later hypervent