Atypical clinical course of ornithine transcarbamylase deficiency due to a new mutant (comparison with Reye's disease)

Abstract

A male infant with ornithine transcarbamylase (OTC) deficiency is described who was relatively symptom free for 4 months, gradually developed severe spasticity due to cerebral atrophy, and died at 13 months of age. Liver OTC activity was 1.5% of the normal mean. The mutant OTC showed an increased apparent Km for ornithine and an increased pH optimum. These kinetic findings fail to explain the atypical clinical course. The clinical picture of patients with genetic OTC deficiency who present during acute exacerbations together with the elevation of serum glutamic oxaloacetic transaminase and microvesicular fat accumulation in liver, as seen in this case, may suggest Reye's syndrome; however, electronmicroscopic examination of this patient suggested that the normal appearance of mitochondria helps to distinguish the two.