A neonate with ornithine aminotransferase deficiency; insights on the hyperammonemia-associated biochemical phenotype of gyrate atrophy

Gyrate atrophy of the choroid and retina (GACR) secondary to deficiency of ornithine aminotransferase (OAT) is a rare autosomal recessive metabolic disorder usually diagnosed in childhood when patients develop myopia and a characteristic retinal degeneration accompanied by hyperornithinemia. Plasma ammonia is normal or sub-normal after the neonatal period. A few GACR patients present in early infancy with hyperammonemia, encephalopathy and a biochemical profile of low plasma ornithine, citrulline and arginine, with increased urinary excretion of homocitrulline and orotic acid, resembling a primary urea cycle disorder. In these patients, ornithine levels do not increase until late infancy or following arginine or citrulline supplementation. We describe a patient with OAT deficiency who presented in the first month of life with episodes of lethargy, vomiting, and hypothermia. He had two episodes of hyperammonemia associated with subnormal levels of plasma ornithine, citrulline and arginine as well as elevated urinary excretion of homocitrulline and orotic acid. Unlike previously reported cases, intermittent hyperornithinemia was observed prior to the first hyperammonemic episode and citrulline supplementation. The latter alleviated the symptoms, normalized ammonia level, and led to increased plasma ornithine concentration. Furthermore, despite a protein restricted diet and ammonia scavenger treatment, continued supplemental citrulline was necessary to prevent hyperammonemia. Molecular analysis confirmed OAT deficiency, differentiating it from proximal urea cycle disorders and deficiency of the mitochondrial ornithine transporter, ORC1, (Hyperammonemia-Hyperornithinemia-Homocitrullinuria syndrome).