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Hyperornithinemia

MedGen UID:
109343
Concept ID:
C0599035
Disease or Syndrome
Synonym: Ornithinemia
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)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM
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 individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
HPO: HP:0012026
OMIM®: 258870

Definition

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.\n\nMost 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.\n\nGyrate 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.\n\nGyrate 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.\n\nIn 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. [from MedlinePlus Genetics]

Clinical features

From HPO
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
EMG abnormality
MedGen UID:
99199
Concept ID:
C0476403
Finding
Abnormal results of investigations using electromyography (EMG).
Abnormality of metabolism/homeostasis
MedGen UID:
867398
Concept ID:
C4021768
Finding
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.\n\nNearsightedness 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.\n\nFor 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.\n\nNearsightedness 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.\n\nEye 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
Inability to see well at night or in poor light.
Blindness
MedGen UID:
99138
Concept ID:
C0456909
Disease or Syndrome
Blindness is the condition of lacking visual perception defined as visual perception below 3/60 and/or a visual field of no greater than 10 degrees in radius around central fixation.
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.
Chorioretinal atrophy
MedGen UID:
884881
Concept ID:
C4048273
Disease or Syndrome
Atrophy of the choroid and retinal layers of the fundus.

Conditions with this feature

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome
MedGen UID:
82815
Concept ID:
C0268540
Disease or Syndrome
Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway. Clinical manifestations and age of onset vary among individuals even in the same family. Neonatal onset (~8% of affected individuals). Manifestations of hyperammonemia usually begin 24-48 hours after feeding begins and can include lethargy, somnolence, refusal to feed, vomiting, tachypnea with respiratory alkalosis, and/or seizures. Infantile, childhood, and adult onset (~92%). 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

Silfverberg T, Sahlander F, Enlund M, Oscarson M, Hårdstedt M
J Med Case Rep 2018 Sep 23;12(1):274. doi: 10.1186/s13256-018-1794-9. PMID: 30243302Free PMC Article
Sokoro AA, Lepage J, Antonishyn N, McDonald R, Rockman-Greenberg C, Irvine J, Lehotay DC
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S275-81. Epub 2010 Jun 24 doi: 10.1007/s10545-010-9148-9. PMID: 20574716
Salvi S, Santorelli FM, Bertini E, Boldrini R, Meli C, Donati A, Burlina AB, Rizzo C, Di Capua M, Fariello G, Dionisi-Vici C
Neurology 2001 Sep 11;57(5):911-4. doi: 10.1212/wnl.57.5.911. PMID: 11552031
Tsujino S, Kanazawa N, Ohashi T, Eto Y, Saito T, Kira J, Yamada T
Ann Neurol 2000 May;47(5):625-31. PMID: 10805333
Nänto-Salonen K, Komu M, Lundbom N, Heinänen K, Alanen A, Sipilä I, Simell O
Neurology 1999 Jul 22;53(2):303-7. doi: 10.1212/wnl.53.2.303. PMID: 10430418

Diagnosis

Martinelli D, Fiermonte G, Häberle J, Boenzi S, Goffredo BM, Travaglini L, Agolini E, Porcelli V, Dionisi-Vici C
Eur J Hum Genet 2020 Jul;28(7):982-987. Epub 2020 Apr 2 doi: 10.1038/s41431-020-0616-x. PMID: 32242103Free PMC Article
Silfverberg T, Sahlander F, Enlund M, Oscarson M, Hårdstedt M
J Med Case Rep 2018 Sep 23;12(1):274. doi: 10.1186/s13256-018-1794-9. PMID: 30243302Free PMC Article
Ono H, Tamada T, Shigematsu Y
Pediatr Int 2018 Aug;60(8):762-764. Epub 2018 Jul 30 doi: 10.1111/ped.13608. PMID: 30058227
Martinelli D, Diodato D, Ponzi E, Monné M, Boenzi S, Bertini E, Fiermonte G, Dionisi-Vici C
Orphanet J Rare Dis 2015 Mar 11;10:29. doi: 10.1186/s13023-015-0242-9. PMID: 25874378Free PMC Article
Kumar K, Agarwal A, Agarwal A, Dhawan A, Chandani N, Raj P
Retin Cases Brief Rep 2015 Spring;9(2):134-7. doi: 10.1097/ICB.0000000000000116. PMID: 25411929

Therapy

Ono H, Tamada T, Shigematsu Y
Pediatr Int 2018 Aug;60(8):762-764. Epub 2018 Jul 30 doi: 10.1111/ped.13608. PMID: 30058227
Tanzer F, Firat M, Alagoz M, Erdogan H
BMJ Case Rep 2011 Mar 15;2011 doi: 10.1136/bcr.07.2010.3200. PMID: 22698901Free PMC Article
Al-Hassnan ZN, Rashed MS, Al-Dirbashi OY, Patay Z, Rahbeeni Z, Abu-Amero KK
J Neurol Sci 2008 Jan 15;264(1-2):187-94. Epub 2007 Sep 7 doi: 10.1016/j.jns.2007.08.003. PMID: 17825324
Dionisi Vici C, Bachmann C, Gambarara M, Colombo JP, Sabetta G
Pediatr Res 1987 Sep;22(3):364-7. doi: 10.1203/00006450-198709000-00025. PMID: 3116497
Giordano C, De Santo NG, Pluvio M, Santinelli R, Stoppoloni G
Nephron 1978;22(1-3):97-106. doi: 10.1159/000181428. PMID: 745643

Prognosis

Silfverberg T, Sahlander F, Enlund M, Oscarson M, Hårdstedt M
J Med Case Rep 2018 Sep 23;12(1):274. doi: 10.1186/s13256-018-1794-9. PMID: 30243302Free PMC Article
Martinelli D, Diodato D, Ponzi E, Monné M, Boenzi S, Bertini E, Fiermonte G, Dionisi-Vici C
Orphanet J Rare Dis 2015 Mar 11;10:29. doi: 10.1186/s13023-015-0242-9. PMID: 25874378Free PMC Article
Sokoro AA, Lepage J, Antonishyn N, McDonald R, Rockman-Greenberg C, Irvine J, Lehotay DC
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S275-81. Epub 2010 Jun 24 doi: 10.1007/s10545-010-9148-9. PMID: 20574716
Tessa A, Fiermonte G, Dionisi-Vici C, Paradies E, Baumgartner MR, Chien YH, Loguercio C, de Baulny HO, Nassogne MC, Schiff M, Deodato F, Parenti G, Rutledge SL, Vilaseca MA, Melone MA, Scarano G, Aldamiz-Echevarría L, Besley G, Walter J, Martinez-Hernandez E, Hernandez JM, Pierri CL, Palmieri F, Santorelli FM
Hum Mutat 2009 May;30(5):741-8. doi: 10.1002/humu.20930. PMID: 19242930
Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD
Pediatr Res 2006 Oct;60(4):423-9. Epub 2006 Aug 28 doi: 10.1203/01.pdr.0000238301.25938.f5. PMID: 16940241

Clinical prediction guides

Sokoro AA, Lepage J, Antonishyn N, McDonald R, Rockman-Greenberg C, Irvine J, Lehotay DC
J Inherit Metab Dis 2010 Dec;33 Suppl 3:S275-81. Epub 2010 Jun 24 doi: 10.1007/s10545-010-9148-9. PMID: 20574716
Amaral AU, Leipnitz G, Fernandes CG, Seminotti B, Zanatta A, Viegas CM, Dutra-Filho CS, Wajner M
Int J Dev Neurosci 2009 Nov;27(7):635-41. Epub 2009 Aug 13 doi: 10.1016/j.ijdevneu.2009.08.004. PMID: 19683047
Camacho JA, Rioseco-Camacho N
Pediatr Res 2009 Jul;66(1):35-41. doi: 10.1203/PDR.0b013e3181a283c1. PMID: 19287344
Tessa A, Fiermonte G, Dionisi-Vici C, Paradies E, Baumgartner MR, Chien YH, Loguercio C, de Baulny HO, Nassogne MC, Schiff M, Deodato F, Parenti G, Rutledge SL, Vilaseca MA, Melone MA, Scarano G, Aldamiz-Echevarría L, Besley G, Walter J, Martinez-Hernandez E, Hernandez JM, Pierri CL, Palmieri F, Santorelli FM
Hum Mutat 2009 May;30(5):741-8. doi: 10.1002/humu.20930. PMID: 19242930
Camacho JA, Mardach R, Rioseco-Camacho N, Ruiz-Pesini E, Derbeneva O, Andrade D, Zaldivar F, Qu Y, Cederbaum SD
Pediatr Res 2006 Oct;60(4):423-9. Epub 2006 Aug 28 doi: 10.1203/01.pdr.0000238301.25938.f5. PMID: 16940241

Recent systematic reviews

Martinelli D, Diodato D, Ponzi E, Monné M, Boenzi S, Bertini E, Fiermonte G, Dionisi-Vici C
Orphanet J Rare Dis 2015 Mar 11;10:29. doi: 10.1186/s13023-015-0242-9. PMID: 25874378Free PMC Article

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