Leigh syndrome (also called Leigh disease and subacute necrotizing encephalomyelopathy) is an inherited neurometabolic disorder that affects the central nervous system. It is named after  Archibald Denis Leigh, a British neuropsychiatrist who first described the condition in 1951. Normal levels of thiamine, thiamine monophosphate, and thiamine diphosphate are commonly found but there is a reduced or absent level of thiamine triphosphate. This is thought to be caused by a blockage in the enzyme thiamine-diphosphate kinase, and therefore treatment in some patients would be to take thiamine triphosphate daily. Signs and symptoms
The symptoms of Leigh syndrome are classically described as beginning in infancy and leading to death within a span of several years; however, as more cases are recognized, it is apparent that symptoms can emerge at any age—including adolescence or adulthood—and patients can survive for many years following diagnosis. Symptoms are often first seen after a triggering event that taxes the bodys energy production, such as an infection or surgery. The general course of Leigh syndrome is one of episodic developmental regression during times of metabolic stress. Some patients have long periods without disease progression while others develop progressive decline.Infants with the syndrome have symptoms that include diarrhea, vomiting, and dysphagia (trouble swallowing or sucking), leading to a failure to thrive. Children with early Leigh disease also may appear irritable and cry much more than healthy babies. Seizures are often seen.
Symptoms of OAT deficiency are progressive, and between the ages of 45 and 65, most affected individuals are almost completely blind.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. 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, 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. 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). 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.