Metabolic follow-up of a Croatian patient with gyrate atrophy and a new mutation in the OAT gene: a case report

Abstract

Gyrate atrophy (GA) of the choroid and retina is a rare autosomal recessive disorder that occurs due to deficiency of the mitochondrial enzyme ornithine aminotransferase (OAT). Hyperornithinemia causes degeneration of the retina with symptoms like myopia, reduced night vision and progressive vision loss. Our patient is a 10-year-old girl with impaired vision and strabismus. As part of the metabolic work-up, plasma amino acid analysis revealed significantly increased concentration of ornithine (1039 μmol/L; reference interval 20 - 155 μmol/L). Molecular genetic analysis revealed homozygous mutation in exon 7 of the OAT gene that has not been reported previously (c.868_870delCTT p.(Leu290del)). This in frame deletion was predicted to be deleterious by in silico software analysis. Our patient was treated with pyridoxine (vitamin B₆ in a dose of 2 x 100 mg/day), low-protein diet (0.6 g/kg/day) and L-lysine supplementation which resulted in a significant reduction in plasma ornithine concentrations to 53% of the initial concentration and the ophthalmologic findings showed significant improvement. We conclude that low protein diet and lysine supplementation can lead to long-term reduction in plasma ornithine concentrations and, if started at an early age, notably slow the progression of retinal function loss in patients with GA. The effect of therapy can be reliably monitored by periodical measurement of plasma ornithine concentration. To our knowledge, this is the first report of OAT deficiency in Croatia.

Keywords: amino acids; ornithinemia; tandem mass spectrometry.

Figure 1

Bilateral cystoid macular oedema - optical coherence tomography (A,B), fluorescein angiography (C,D) and peripheral fundus with numerous circular sharply limited atrophic zones in the retina - fluorescein angiography (E,F).

Figure 2

High intensity peak of ornithine (Orn) was found by comparing the patient’s plasma amino acid chromatogram (A) with a chromatogram of the internal standard (B).

Figure 3

Monitoring of plasma amino acid concentration during dosage adjustment. Ornithine values significantly differed between the first and third period of treatment.