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We report an ornithine transcarbamylase(OTC)-deficient male patient who had no detectable immunoreactive materials but did have active mRNA for OTC-related protein. The total absence of OTC activity in the liver of the patient was caused by a complete lack of immunoreactive material, as determined by Ouchterlony double immunodiffusion, single radial immunodiffusion, and sodium dodecylsulphate-polyacrylamide gel electrophoresis of immunoprecipitate and of liver homogenate.

Abstract: Argininosuccinate (ASA) synthetase in the liver from a patient with a variant form of citrullinaemia was analysed. Serum citrulline level was approximately 40 times higher than the control level, and the ASA synthetase activity was approximately 10% that of the control. Other urea cycle enzymes were within normal ranges. The specific activity (enzyme activity/enzyme protein, measured by immunochemical method), pH optimum, Michaelis constants, and thermal denaturation in the presence or absence of ASA were similar to those in enzymes obtained from the normal and the patient's liver cells. Noin vitro effect of the patient's liver homogenate on ASA synthetase in normal liver was observed. Serum citrulline levels of the patient's parents and young brother were at the maximal level of control at fasting and definitely elevated 4 h after citrulline loading (100 mg/kg).

A 24-year-old patient had symptoms of lethargy, convulsions and hyperammonaemia during valproic acid therapy. Cessation of valproic acid treatment brought about an improvement both of the symptoms and of the hyperammonaemia. However, enzymatic analysis after the cessation of valproic acid therapy revealed a complete absence of carbamoylphosphate synthetase (CPS) activity in liver biopsy. A unique polypeptide band, corresponding to the control CPS protein in molecular weight (‘CPS-like’ protein), was found in normal amounts in the patient's liver on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. This CPS-like protein seemed to be more labile than the control, because the polypeptide band became faint after freeze-thawing. Intravenous administration ofl-alanine resulted in a significant increase of serum urea and a transient increase of blood ammonia concentrations. These results strongly suggest that the patient has a labile CPS protein with no activityin vitro but some activityin vivo. We consider that valproic acid may have disrupted some metabolic adaptation by reducingN-acetylglutamate in the liver, which in combination with CPS deficiency induced severe hyperammonaemia.