While we and others have successfully cured the spf(ash) mouse model of OTC deficiency using adeno-associated virus (AAV) vectors, a major limitation of this model is the presence of residual OTC enzymatic activity which confers a mild phenotype without clinically significant hyperammonemia.
Male spf <sup>ash</sup> mice have a mild biochemical phenotype with low OTC activity (5%-10% of wild-type), resulting in elevated urinary orotic acid but no hyperammonemia.
These data show that the distribution of OTC activity within the liver is critical and that rAAV vector re-delivery after early neonatal treatment is likely to be necessary for stable control of hyperammonaemia into adulthood.
Three of the patients showed decreased ornithine transcarbamylase activity in liver obtained by needle biopsy, and the other two had marked orotic aciduria associated with hyperammonemia.
Here we present the case of a previously asymptomatic 24-year-old woman who died of severe hyperammonemia associated with orotic aciduria but normal OTC activity in the fourth month of pregnancy.
The activities of the urea cycle enzymes in the liver of a female patient with hyperammonemia were determined (Table 1).Ornithine transcarbamylase (OTC, EC.
Ornithine transcarbamylase (OTC) deficiency (McKusick 311250), an X-linked inherited disorder, often presents in males with severe neonatal onset of hyperammonemia.
We tested the hypothesis that female carriers of ornithine transcarbamylase (OTC) deficiency have cerebral dysfunction as a consequence of episodic hyperammonemia.
The aims of this report are to 1) present a rare case of fatal cerebral edema associated with late-onset ornithine transcarbamylase (OTC) deficiency in a juvenile male patient receiving valproic acid and 2) review the neuropathologic changes associated with the hyperammonemia.
Diagnosis of ornithine transcarbamylase (OTC) deficiency was made on the basis of hyperammonaemia, hypocitrullinaemia and extreme hyperexcretion of orotic acid.
Ornithine transcarbamylase (OTC) deficiency is a frequent X linked disorder of the urea cycle which is responsible for lethal neonatal hyperammonaemia in males and for various clinical symptoms in heterozygous females.
Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle in humans and is responsible for lethal neonatal hyperammonemia in males.