Ornithine aminotransferase deficiency (also known as gyrate atrophy of the choroid and retina) is an inborn error of

ornithine Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl. Role in urea cycle L-Ornithine is one of the produ ...

metabolism, caused by decreased activity of the

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

ornithine aminotransferase Ornithine aminotransferase (OAT) is an enzyme which is encoded in human by the OAT gene located on chromosome 10. The OAT involved in the ultimate formation of the non-essential amino acid proline from the amino acid ornithine. Ornithine aminot ...

. Biochemically, it can be detected by elevated levels of ornithine in the blood. Clinically, it presents initially with poor

night vision Night vision is the ability to see in low-light conditions, either naturally with scotopic vision or through a night-vision device. Night vision requires both sufficient spectral range and sufficient intensity range. Humans have poor night vi ...

, which slowly progresses to total blindness. It is believed to be inherited in an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

manner. Approximately 200 known cases have been reported in the literature. The incidence is highest in

Finland Finland ( fi, Suomi ; sv, Finland ), officially the Republic of Finland (; ), is a Nordic country in Northern Europe. It shares land borders with Sweden to the northwest, Norway to the north, and Russia to the east, with the Gulf of B ...

, 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 Creatine ( or ) is an organic compound with the nominal formula (H2N)(HN)CN(CH3)CH2CO2H. It exists in various modifications (tautomers) in solution. Creatine is found in vertebrates where it facilitates recycling of adenosine triphosphate ( ...

often found in this population. Treatment may include

vitamin B6 Vitamin B6 is one of the B vitamins, and thus an essential nutrient. The term refers to a group of six chemically similar compounds, i.e., "vitamers", which can be interconverted in biological systems. Its active form, pyridoxal 5′-phosphat ...

lysine Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −C ...

or dramatic dietary change to minimise

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) and both the am ...

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 Near-sightedness, also known as myopia and short-sightedness, is an eye disease where light focuses in front of, instead of on, the retina. As a result, distant objects appear blurry while close objects appear normal. Other symptoms may include ...

which progresses to

night blindness Nyctalopia (; ), also called night-blindness, is a condition making it difficult or impossible to see in relatively low light. It is a symptom of several eye diseases. Night blindness may exist from birth, or be caused by injury or malnutrition ( ...

. The onset of myopia is often in early childhood.

Ophthalmological Ophthalmology ( ) is a surgical subspecialty within medicine that deals with the diagnosis and treatment of eye disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a medic ...

findings in affected individuals include constricted visual fields, posterior subcapsular

cataracts A cataract is a cloudy area in the lens of the eye that leads to a decrease in vision. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colors, blurry or double vision, halos around light, trouble w ...

(can begin in late teens), elevated

dark adaptation threshold {{unreferenced, date=January 2015 Dark Adaptation Threshold (DAT) is a Visual perception, vision test that measures the adjustment of the eye occurring under low levels of illumination. When light enters the eye, it ultimately reaches the rods and c ...

s and decreased or absent electroretinographic responses. 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 Ornithine transcarbamylase deficiency also known as OTC deficiency is the most common urea cycle disorder in humans. Ornithine transcarbamylase, the defective enzyme in this disorder is the final enzyme in the proximal portion of the urea cycle, re ...

, as the block in ornithine metabolism leads to secondary dysfunction of the

urea cycle The urea cycle (also known as the ornithine cycle) is a cycle of biochemical reactions that produces urea (NH2)2CO from ammonia (NH3). Animals that use this cycle, mainly amphibians and mammals, are called ureotelic. The urea cycle converts highl ...

. These individuals present with

hyperammonemia Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to brain injury and death. It may be primary or secondary. Ammonia is a substance that contains nitrogen. It i ...

, poor feeding, failure to thrive and increased excretion of orotic acid.

Genetics

OAT deficiency is inherited in an

manner, meaning an affected individual must inherit a mutated

allele An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution. ::"The chro ...

from both parents. The enzyme,

is coded for by the

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

''OAT'', located at 10q26. OAT deficiency has an increased incidence in

, and this population has a common

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

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 Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

concentrations in

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

, in search of a significantly elevated

concentration. Measurement of

urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

amino acid concentrations is sometimes necessary, particularly in neonatal onset cases to identify the presence or absence of

homocitrulline L-Homocitrulline is an amino acid and a metabolite of ornithine in mammalian (including human) metabolism. The amino acid can be detected in larger amounts in the urine of individuals with urea cycle disorders. At present, it is thought that th ...

for ruling out

ornithine translocase deficiency Ornithine translocase deficiency, also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, is a rare autosomal recessive urea cycle disorder affecting the enzyme ornithine translocase, which causes ammonia to accumulate in ...

(hyperornithinemia, hyperammonemia, homocitrullinuria syndrome, HHH syndrome). Ornithine concentrations can be an unreliable indicator in the newborn period, thus

newborn screening Newborn screening (NBS) is a public health program of screening in infants shortly after birth for conditions that are treatable, but not clinically evident in the newborn period. The goal is to identify infants at risk for these conditions earl ...

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 A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells o ...

lymphoblasts __NOTOC__ A lymphoblast is a modified naive lymphocyte with altered cell morphology. It occurs when the lymphocyte is activated by an antigen (from antigen-presenting cells) and increased in volume by nucleus and cytoplasm growth as well as new mRN ...

for confirmation or during the neonatal period when the results of biochemical testing is unclear. Molecular genetic testing is also an option.

Treatment

To reduce the levels of ornithine in the blood, a diet restricted in arginine has been used. Some research has shown that when diet or other treatment is initiated early in life, the outcome can be improved.

References

External links

{{Medical resources , DiseasesDB = , ICD10 = , ICD9 = , ICDO = , OMIM = 258870 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = Inborn errors of metabolism Amino acid metabolism disorders Autosomal recessive disorders