Rare genetic disorder affecting mitochondrial metabolism of
ornithine. It is characterized by the presence of gyrate atrophy of the
retina leading to night blindness that begins in late childhood, accompanied
by sharply demarcated circular areas of chorioretinal atrophy. The areas of
atrophy enlarge during the second and third decades. Posterior subcapsular
cataracts have been associated by the end of the second decade. Computed
tomography and magnetic resonance imaging (MRI) studies demonstrated the presence of type II muscle fiber
changes in large muscle groups because of hyperornithinemia-induced
deficiency of high-energy creatine phosphate. Brain MRI revealed
degenerative lesions in the white matter in 50% of the gyrate atrophy
patients, and 70% present premature atrophic changes. Early degenerative,
atrophic brain changes and abnormal EEG are features of gyrate atrophy, in
addition to the well-characterized eye and muscle manifestations.
OAT Deficiency; Hyperornithinemia Gyrate Atrophy of the
Choroid and Retina.
Genetic disorder leading to visual disturbances caused by
progressive chorioretinal atrophy.
Autosomal recessive transmission; high
incidence in the Finnish population. The gene has been mapped on chromosome
OAT is a mitochondrial enzyme requiring pyridoxal
phosphate. In the neonatal period, the role of OAT reaction is to synthesize
ornithine to produce arginine via citrulline; later, the role of OAT is to
catabolize excess ornithine generated from dietary arginine. The cause of
chorioretinal degeneration could be insufficient proline synthesis from
ornithine in the retinal pigment epithelium.
Plasma ornithine levels more than 10 to 20 times normal.
Diagnosis usually established by specialized ophthalmologic examination.
Night blindness and myopia in early childhood are
the first symptoms. Retinopathy can be detected at electroretinography
before visual disturbances are obvious. Chorioretinal atrophy can be detected at
funduscopy. Considerable differences in severity of the disease. Subcapsular
cataracts at the end of the second decade of life. Blindness caused by
chorioretinal atrophy between 40 and 50 years of age in patients
unresponsive to pyridoxine. Muscle pathology with type II fiber atrophy and
tubular aggregates in some patients. Treatment consists of pharmacological
doses of pyridoxine (vitamin B6) and/or a low-arginine diet.
No specific precautions before
anesthesia except for the surgical procedure involved.
Individual affected might be visually
impaired or blind. Bright operating room will provide reassurance. The
presence of muscle atrophy or dysfunction should be considered when using
neuromuscular blocking agents.
No known implication between
anesthesia medication and administration of large doses of vitamin B6.
HHH Syndrome: Resembles ornithinemia with gyrate atrophy except
there are no visual problems or fundus changes. The pathophysiology involves
diminished ornithine transport into mitochondria, resulting in ornithine
accumulation in the cytoplasm and reduced ability to clear carbamoyl
phosphate and ammonia loads. Autosomal recessive inheritance has been
Shih VE, Stöckler-Ipsiroglu S: Disorders of ornithine and creatine
metabolism, in Fernandes J, Saudubray J-M, van den Berghe G ...