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. Clinically, it presents initially with poor night vision, which slowly progresses to total blindness. 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.Research suggests there can be some adverse effect on muscles and also the brain. The cause of this is somewhat unclear but may relate to very low levels of creatine often found in this population. Treatment may include vitamin B6, lysine or dramatic dietary change to minimise arginine from patients diet. Research has indicated that these treatments may be somewhat effective in lowering ornithine blood concentration levels in some patients, either in combination or individually. Vitamin B6 has been found to be very effective in a small proportion of patients. 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.
Zidovudine (AZT) or tenofovir (TDF) are recommended as less toxic and equally effective alternatives." Mechanism of action
Stavudine is a nucleoside analog of thymidine. It is phosphorylated by cellular kinases into an active triphosphate. Stavudine triphosphate inhibits HIVs reverse transcriptase by competing with the natural substrate, thymidine triphosphate. Reverse transcriptase is the enzyme the virus uses to make a DNA copy of its RNA in order to insert its genetic material into the hosts DNA. Upon incorporation into the DNA strand, stavudine triphosphate causes termination of DNA replication. Pharmacokinetics
Absorption: Stavudine has rapid absorption and good oral bioavailability  (F = 0.86).Distribution: Stavudine does not bind to proteins in the blood.Metabolism: The clearance of stavudine is affected minimally by hepatic metabolism. Oxidation and glucuronidation produce minor metabolites.Elimination: Stavudine is mostly eliminated in the urine and mostly in its unchanged form. Drug interactions
Simultaneous use of zidovudine is not recommended, as it can inhibit the intracellular phosphorylation of stavudine. Other anti-HIV drugs do not possess this property. Stavudine is not protein-bound nor does it inhibit the major cytochrome P450 isoforms. Thus, significant drug interactions with drugs metabolized through these pathways or drugs that are protein-bound are unlikely. History
Stavudine was first created by Jerome Horwitz in the 1960s and was originally named D4T. When the AIDS epidemic occurred in the 1980s, William Prusoff and Dr. Tai-Shun Lin discovered the anti-HIV properties of Stavudine.