Ornithine Aminotransferase Deficiency in Differential Diagnosis of Neonatal Hyperammonemia: A Case with a Novel OAT Gene Mutation.

Abstract

To the Editor: Ornithine aminotransferase (OAT) deficiency is a rare metabolic disorder characterized by gyrate atrophy of choroid and retina resulting in loss of all functional vision between fourth to sixth decades [1]. Rarely, neonates with OAT deficiency can present with hyperammonemia [2]. Here, a patient who was diagnosed as OAT deficiency with a rare presentation of symptomatic neonatal hyperammonemia is reported. Diagnosis was confirmed with a novel OAT gene mutation. A female patient, born at term from consanguineous parents developed vomiting and abnormal cycling movements at 18 d of age. Physical examination revealed reduced level of consciousness, increased deep tendon reflexes and hypertonicity. Her plasma ammonia level was measured as 280 μmol/L. She was treated with intravenous sodium benzoate and arginine and enteral feeding was discontinued. Plasma ammonia level fell to normal ranges within 4 h. Initial metabolic investigations revealed elevated plasma glutamine levels whereas plasma ornithine and citrulline levels were remarkably reduced (Table 1). Acylcarnitine profile and urinary organic acid analysis were unremarkable. Urinary orotic acid excretion was normal. Oral sodium benzoate and arginine supplementation were started as a maintenance therapy and patient was fed by a low-protein diet. In follow-up she had no further episodes of hyperammonemia. By 3 mo of age, a rise in plasma ornithine level was detected (Table 1). Urinary homocitrulline excretion was normal. Depending on increased ornithine levels accompanied by normal urinary homocitrulline excretion; diagnosis of ornithine aminotransferase (OAT) deficiency was suspected. Molecular analysis of OAT gene demonstrated homozygote mutation for IVS7-1G>A (c.901-1G>A) which has not been reported before (Fig. 1). Depending on OAT deficient mouse model, Wang et al. explained different physiologic functions of OAT enzyme at different developmental stages. In the neonatal period, the main role of the enzyme is ornithine synthesis and maintenance of urea cycle by converting glutamine to arginine, whereas in different developmental stages its role is ornithine degradation and deficiency of the enzyme causes hyperornithinemia and retinal toxicity [3]. In literature, there are a few reports about neonatal OAT deficiency [2–5]. As early diagnosis of disease may prevent the ophthalmological findings, OAT deficiency should be considered in differential diagnosis of neonatal hyperammonemia. * Tanyel Zubarioglu tanyel0554@yahoo.com