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Importance of measuring amino acid concentrations on tandem mass spectrometer in follow-up treatment of ornithinemia: a case report

Introduction Gyrate atrophy of the choroid and retina (OMIM: 258870) is a rare autosomal recessive disease that occurs due to the lack of the mitochondrial enzyme ornithine aminotransferase (OAT ; EC 2.6.1.13). Hyperornithinemia causes degeneration of the retina with the symptoms of disease like myopia, reduction in night vision and progressive resolution of vision loss. Our patient is an 8- year-old girl with impaired vision and strabismus. First symptoms appeared at the age of four years. Further ophthalmic examination revealed retinal dystrophy and macular edema in both eyes, with numerous circular sharply limited zones in the retina. The characteristic ophthalmologic finding was suspected on deficiency of an enzyme OAT involved in the metabolism of the amino acid ornithine. Materials and methods Amino acid analysis was performed using high-performance liquid chromatography coupled with electrospray tandem mass spectrometry LC-MS/MS (API 3200, Sciex ; UPLC Nexera, Shimadzu). Using aTRAQ™ kit for physiological amino acid analysis allows quantitation of free amino acids in plasma. Analyst and Cliqid software applications (Sciex) were used to obtain data for relative and absolute quantitation of up to 45 amino acids. Results As part of the metabolic check-up, analysis of amino acids in plasma revealed significantly increased concentration of ornithine (1039 µmol/L ; normal: 20-155 µmol/L). Molecular genetic analysis detected the homozygous mutation in exon 7 of the OAT gene that has not been described as yet (c.868_870delCTT p.Leu290del ; Zurich Children's Hospital). The success of low-protein diet and response to pyridoxine (initial dose of 500 mg with poor response) was monitored by measuring ornithine concentration for more than one year. Plasma ornithine levels decreased by 30-40% (fell to 608 µmol/L). Our expectation from including a recent therapy with L-lysine is to reduce reabsorption of arginine and ornithine in the kidney tubules. Conclusion Hyperornithinemia is the main pathogenic factor in gyrate atrophy and can be influenced by diet. LC-MS/MS is one of the best methods for diagnosing, treatment and follow- up of hyperornithinemia.

Ornithinemia ; Amino acid analysis ; LC-MS/MS ; Gyrate atrophy

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