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Ornithine aminotransferase deficiency(GACR)

MedGen UID:
109343
Concept ID:
C0599035
Disease or Syndrome
Synonyms: GACR; Girate atrophy of the retina; Gyrate atrophy; Gyrate atrophy of choroid and retina; High blood ornithine levels; Hyperornithinemia; Hyperornithinemia with gyrate atrophy of choroid and retina; OAT deficiency; OKT deficiency; Ornithine ketoacid aminotransferase deficiency
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). [HPO:curators]
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Deficiency of ornithine-oxo-acid aminotransferase (276426004); Ornithine oxo-acid aminotransferase deficiency (276426004); Ornithine aminotransferase deficiency (276426004); Ornithine ketoacid transaminase deficiency (276426004); OKT deficiency (276426004); Ornithine-oxo-acid amino acid transferase deficiency (276426004); Ornithine-delta-aminotransferase deficiency (276426004); OAT - Ornithine oxo-acid aminotransferase deficiency (276426004); OAT deficiency (276426004); Hyperornithinemia (33985005)
 
Gene (location): OAT (10q26.13)
OMIM®: 258870
HPO: HP:0012026

Definition

Gyrate atrophy of the choroid and retina due to deficiency of ornithine aminotransferase is clinically characterized by a triad of progressive chorioretinal degeneration, early cataract formation, and type II muscle fiber atrophy. Characteristic chorioretinal atrophy with progressive constriction of the visual fields leads to blindness at the latest during the sixth decade of life. Patients generally have normal intelligence (summary by Peltola et al., 2002). See 238970 for another hyperornithinemia syndrome. [from OMIM]

Additional description

From GHR
Gyrate atrophy of the choroid and retina, which is often shortened to gyrate atrophy, is an inherited disorder characterized by progressive vision loss. People with this disorder have an ongoing loss of cells (atrophy) in the retina, which is the specialized light-sensitive tissue that lines the back of the eye, and in a nearby tissue layer called the choroid. During childhood, they begin experiencing nearsightedness (myopia), difficulty seeing in low light (night blindness), and loss of side (peripheral) vision. Over time, their field of vision continues to narrow, resulting in tunnel vision. Many people with gyrate atrophy also develop clouding of the lens of the eyes (cataracts). These progressive vision changes lead to blindness by about the age of 50.Most people with gyrate atrophy have no symptoms other than vision loss, but some have additional features of the disorder. Occasionally, newborns with gyrate atrophy develop excess ammonia in the blood (hyperammonemia), which may lead to poor feeding, vomiting, seizures, or coma. Neonatal hyperammonemia associated with gyrate atrophy generally responds quickly to treatment and does not recur after the newborn period.Gyrate atrophy usually does not affect intelligence; however, abnormalities may be observed in brain imaging or other neurological testing. In some cases, mild to moderate intellectual disability is associated with gyrate atrophy.Gyrate atrophy may also cause disturbances in the nerves connecting the brain and spinal cord to muscles and sensory cells (peripheral nervous system). In some people with the disorder these abnormalities lead to numbness, tingling, or pain in the hands or feet, while in others they are detectable only by electrical testing of the nerve impulses.In some people with gyrate atrophy, a particular type of muscle fibers (type II fibers) break down over time. While this muscle abnormality usually causes no symptoms, it may result in mild weakness.  https://ghr.nlm.nih.gov/condition/gyrate-atrophy-of-the-choroid-and-retina

Clinical features

Myopia
MedGen UID:
44558
Concept ID:
C0027092
Disease or Syndrome
Nearsightedness, also known as myopia, is an eye condition that causes blurry distance vision. People who are nearsighted have more trouble seeing things that are far away (such as when driving) than things that are close up (such as when reading or using a computer). If it is not treated with corrective lenses or surgery, nearsightedness can lead to squinting, eyestrain, headaches, and significant visual impairment.Nearsightedness usually begins in childhood or adolescence. It tends to worsen with age until adulthood, when it may stop getting worse (stabilize). In some people, nearsightedness improves in later adulthood.For normal vision, light passes through the clear cornea at the front of the eye and is focused by the lens onto the surface of the retina, which is the lining of the back of the eye that contains light-sensing cells. People who are nearsighted typically have eyeballs that are too long from front to back. As a result, light entering the eye is focused too far forward, in front of the retina instead of on its surface. It is this change that causes distant objects to appear blurry. The longer the eyeball is, the farther forward light rays will be focused and the more severely nearsighted a person will be.Nearsightedness is measured by how powerful a lens must be to correct it. The standard unit of lens power is called a diopter. Negative (minus) powered lenses are used to correct nearsightedness. The more severe a person's nearsightedness, the larger the number of diopters required for correction. In an individual with nearsightedness, one eye may be more nearsighted than the other.Eye doctors often refer to nearsightedness less than -5 or -6 diopters as "common myopia." Nearsightedness of -6 diopters or more is commonly called "high myopia." This distinction is important because high myopia increases a person's risk of developing other eye problems that can lead to permanent vision loss or blindness. These problems include tearing and detachment of the retina, clouding of the lens (cataract), and an eye disease called glaucoma that is usually related to increased pressure within the eye. The risk of these other eye problems increases with the severity of the nearsightedness. The term "pathological myopia" is used to describe cases in which high myopia leads to tissue damage within the eye.
Nyctalopia
MedGen UID:
10349
Concept ID:
C0028077
Disease or Syndrome
An inability to see clearly in dim light; due to a deficiency of vitamin A or to a retinal disorder.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Finding
Blindness is the condition of lacking visual perception due to physiological or neurological factors.
EMG abnormality
MedGen UID:
99199
Concept ID:
C0476403
Finding
Abnormal results of investigations using electromyography (EMG).
Chorioretinal atrophy
MedGen UID:
99273
Concept ID:
C0521683
Disease or Syndrome
Atrophy of the choroid and retinal layers of the fundus.
Posterior subcapsular cataract
MedGen UID:
163646
Concept ID:
C0858617
Disease or Syndrome
A type of cataract affecting the posterior pole of lens immediately adjacent to ('beneath') the Lens capsule.
Proximal muscle weakness
MedGen UID:
325534
Concept ID:
C1838869
Sign or Symptom
A lack of strength of the proximal muscles.
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVOrnithine aminotransferase deficiency
Follow this link to review classifications for Ornithine aminotransferase deficiency in Orphanet.

Conditions with this feature

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
MedGen UID:
82815
Concept ID:
C0268540
Disease or Syndrome
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is characterized by variable clinical presentation and age of onset. Neonatal onset (~12% of affected individuals). Infants are normal for the first 24-48 hours followed by onset of symptoms related to hyperammonemia (poor feeding, vomiting, lethargy, low temperature, rapid breathing). Information on long-term outcome is limited. Infancy, childhood, and adult presentation (~88%). Affected individuals may present with: Chronic neurocognitive deficits (including developmental delay, ataxia, spasticity, learning disabilities, cognitive deficits and/or unexplained seizures); Acute encephalopathy secondary to hyperammonemic crisis precipitated by a variety of factors; and Chronic liver dysfunction (unexplained elevation of liver transaminases with or without mild coagulopathy, with or without mild hyperammonemia and protein intolerance). Neurologic findings and cognitive abilities can continue to deteriorate despite early metabolic control that prevents hyperammonemia.

Recent clinical studies

Etiology

Vatanavicharn N, Ratanarak P, Liammongkolkul S, Sathienkijkanchai A, Wasant P
Clin Chim Acta 2012 Jul 11;413(13-14):1141-4. Epub 2012 Mar 23 doi: 10.1016/j.cca.2012.03.014. PMID: 22465081
Mehta MC, Katsumi O, Shih VE, Hirose T
Acta Ophthalmol (Copenh) 1991 Dec;69(6):810-4. PMID: 1789102

Diagnosis

Vatanavicharn N, Ratanarak P, Liammongkolkul S, Sathienkijkanchai A, Wasant P
Clin Chim Acta 2012 Jul 11;413(13-14):1141-4. Epub 2012 Mar 23 doi: 10.1016/j.cca.2012.03.014. PMID: 22465081
Santos L, Fiona WJ, Walter JH
J Inherit Metab Dis 2006 Feb;29(1):240. doi: 10.1007/s10545-006-0286-z. PMID: 16601905
Cleary MA, Dorland L, de Koning TJ, Poll-The BT, Duran M, Mandell R, Shih VE, Berger R, Olpin SE, Besley GT
J Inherit Metab Dis 2005;28(5):673-9. doi: 10.1007/s10545-005-0074-1. PMID: 16151897
Ohkubo Y, Ueta A, Ito T, Sumi S, Yamada M, Ozawa K, Togari H
Tohoku J Exp Med 2005 Apr;205(4):335-42. PMID: 15750329
Mehta MC, Katsumi O, Shih VE, Hirose T
Acta Ophthalmol (Copenh) 1991 Dec;69(6):810-4. PMID: 1789102

Therapy

Santos L, Fiona WJ, Walter JH
J Inherit Metab Dis 2006 Feb;29(1):240. doi: 10.1007/s10545-006-0286-z. PMID: 16601905

Prognosis

Mehta MC, Katsumi O, Shih VE, Hirose T
Acta Ophthalmol (Copenh) 1991 Dec;69(6):810-4. PMID: 1789102

Clinical prediction guides

Ohkubo Y, Ueta A, Ito T, Sumi S, Yamada M, Ozawa K, Togari H
Tohoku J Exp Med 2005 Apr;205(4):335-42. PMID: 15750329
Ramesh V, Gusella JF, Shih VE
Mol Biol Med 1991 Feb;8(1):81-93. PMID: 1682785
Vannas-Sulonen K, Vannas A, O'Donnell JJ, Sipilä I, Wood I
Acta Ophthalmol (Copenh) 1983 Feb;61(1):9-19. PMID: 6858648

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