Ornithine aminotransferase deficiency

Ornithine aminotransferase deficiency
Ornithine
Classification and external resources
OMIM	258870

Ornithine aminotransferase deficiency (also known as gyrate atrophy of the choroid and retina) is an inborn error of ornithine metabolism, caused by decreased activity of the enzyme ornithine aminotransferase. Biochemically, it can be detected by elevated levels of ornithine in the blood.^[1] Clinically, it presents initially with poor night vision, which slowly progresses to total blindness.^[2] It is believed to be inherited in an autosomal recessive manner. Approximately 200 known cases have been reported in the literature. The incidence is highest in Finland, estimated at 1:50,000.^[2]

Clinical presentation

Quite often, the presenting symptom of ornithine aminotransferase (OAT) deficiency is myopia which progresses to night blindness. The onset of myopia is often in early childhood. Ophthalmological findings in affected individuals include constricted visual fields, posterior subcapsular cataracts (can begin in late teens), elevated dark adaptation thresholds and decreased or absent electroretinographic responses.^[3] Symptoms of OAT deficiency are progressive, and between the ages of 45 and 65, most affected individuals are almost completely blind.^[3]

In some cases, affected individuals will present in the neonatal period with disease that closely mimics a classic urea cycle defect, such as ornithine transcarbamylase deficiency, as the block in ornithine metabolism leads to secondary dysfunction of the urea cycle. These individuals present with hyperammonemia, poor feeding, failure to thrive and increased excretion of orotic acid.^[3]

Diagnosis

Upon clinical suspicion, diagnostic testing will often consist of measurement of amino acid concentrations in plasma, in search of a significantly elevated ornithine concentration. Measurement of urine amino acid concentrations is sometimes necessary, particularly in neonatal onset cases to identify the presence or absence of homocitrulline for ruling out ornithine translocase deficiency (hyperornithinemia, hyperammonemia, homocitrullinuria syndrome, HHH syndrome).^[3] Ornithine concentrations can be an unreliable indicator in the newborn period, thus newborn screening may not detect this condition, even if ornithine is included in the screening panel. Enzyme assays to measure the activity of ornithine aminotransferase can be performed from fibroblasts or lymphoblasts for confirmation or during the neonatal period when the results of biochemical testing is unclear.^[3] Molecular genetic testing is also an option.^[3]

Genetics

OAT deficiency is inherited in an autosomal recessive manner, meaning an affected individual must inherit a mutated allele from both parents. The enzyme, ornithine aminotransferase is coded for by the gene OAT, located at 10q26. OAT deficiency has an increased incidence in Finland,^[2] and this population has a common mutation accounting for more than 85% of mutant alleles in this population. It has not been described in any other populations.^[3]

References

1. "Gyrate atrophy of the choroid and retina". National Institutes of Health. Retrieved 2012-08-23.
2. "#288870 - Gyrate atrophy of the choroid and retina". Johns Hopkins University. Retrieved 2012-08-23.
3. Baumgartner, Matthias R.; Valle, David (2012). "Disorders of Ornithine Metabolism". In Saudubray, Jean-Marie; van den Berghe, Georges; Walter, John H. Inborn Metabolic Diseases: Diagnosis and Treatment (5th ed.). New York: Springer. pp. 323–332. ISBN 978-3-642-15719-6.