Albinism pathophysiology: Difference between revisions

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{{CMG}}; {{AE}} {{S.M}}
{{CMG}}; {{AE}} {{S.M}}
==Overview==
==Overview==
[[Melanocytes]] are derived from [[neural crest]] [[ectoderm]] and are found in [[hair follicles]], [[skin]], [[eyes]], and [[inner ear]]. [[Melanocytes]] produce [[melanin]] which protects [[skin]] from [[ultraviolet]]. [[Tyrosinase]] converts [[tyrosine]] to [[DOPA]], [[dopaquinone]], and then [[melanin]]. [[Mutation]] in [[Tyrosinase]] [[enzyme]] is responsible for causing [[albinism]]. Additionally, [[melanin]] is responsible for development of the [[fovea]], [[optic nerves]], [[optic tracts]], and [[visual cortex]].Decussation of some optic nerve fibers at [[optic chiasm]] are essential for binocular vision. However, in [[albinism]], most of [[nerve fibers]] decussate at [[optic chiasm]] and cause monocluar vision presented as [[strabismus]]. In [[ocular albinism]], [[macular]] pigment is absent and [[fovea]] [[hypoplasia]] leads to decreased [[visual acuity]].


==Pathophysiology==
==Pathophysiology==
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* [[Melanin]] protects [[skin]] from [[ultraviolet]]; with [[sun]] exposure [[melanin]] pigment increases in the [[skin]]
* [[Melanin]] protects [[skin]] from [[ultraviolet]]; with [[sun]] exposure [[melanin]] pigment increases in the [[skin]]
* Apart from the photo-protective effect of [[melanin]], it has some roles in the development of [[ocular]] structures as well as [[oculoneural]] pathways
* Apart from the photo-protective effect of [[melanin]], it has some roles in the development of [[ocular]] structures as well as [[oculoneural]] pathways
* [[Melanin]] converts tyrosine to 2 forms named [[eumelanin]] and [[pheomelanin]]
* [[Melanin]] converts 2 forms named [[eumelanin]] and [[pheomelanin]]
* [[Eumelanin]] is responsible for black or brown [[skin]] color and protects [[skin]] from [[ultraviolet]] B
* [[Eumelanin]] is responsible for black or brown [[skin]] color and protects [[skin]] from [[ultraviolet]] B
* [[Pheomelanin]] is responsible for red or blond hair and light-colored, and ruddy s[[kin]]
* [[Pheomelanin]] is responsible for red or blond hair and light-colored, and ruddy s[[kin]]
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*  [[Mutation]] in [[Tyrosinase]] [[enzyme]] is responsible for causing [[albinism]]
*  [[Mutation]] in [[Tyrosinase]] [[enzyme]] is responsible for causing [[albinism]]
*  [[Tyrosinase]] converts [[tyrosine]] to [[DOPA]] and then [[dopaquinone]]; subsequenstly, [[dopaquionone]] converts to either [[eumelanin]] or [[pheomelanin]]
*  [[Tyrosinase]] converts [[tyrosine]] to [[DOPA]] and then [[dopaquinone]]; subsequenstly, [[dopaquionone]] converts to either [[eumelanin]] or [[pheomelanin]]
*  [[Tyrosinase]] mutation is seen in [[oculocutaneous albinism]] 1 ([[OCA1]]) and [[autosomal-recessive]] [[ocular albinism]] ([[AROA]])
*  [[Tyrosinase]] mutation is seen in [[oculocutaneous albinism]] 1 (OCA1) and [[autosomal-recessive]] [[ocular albinism]] (AROA)
*  Lack of [[melanin]] increase chances of sun-damage related diseases including [[actinic keratosis]] and UV-related [[malignancies]]
*  Lack of [[melanin]] increase chances of sun-damage related diseases including [[actinic keratosis]] and UV-related [[malignancies]]
* [[Ocular]] [[albinism]] pathway:
* [[Ocular]] [[albinism]] pathway:
** In [[uterus]], [[melanin]] is responsible for developement of the [[fovea]], [[optic nerves]], [[optic tracts]], and [[visual cortex]]
** In [[uterus]], [[melanin]] is responsible for development of the [[fovea]], [[optic nerves]], [[optic tracts]], and [[visual cortex]]
** Decussation of some optic nerve fibers at [[optic chiasm]] are essential for binocular vision
** Decussation of some optic nerve fibers at [[optic chiasm]] are essential for binocular vision
** In people without [[albinism]], about 45% of [[optic nerve]] fibers from the [[temporal]] part of [[retina]] do not cross the [[optic chiasem]] to [[controlateral]] [[lateral geniculate nucleus]]   
** In people without [[albinism]], about 45% of [[optic nerve]] fibers from the [[temporal]] part of [[retina]] do not cross the [[optic chiasem]] to [[controlateral]] [[lateral geniculate nucleus]]   
** In [[albinism]], most of [[nerve fibers]] decussate at [[optic chiasm]] and cause monocluar vision
** In [[albinism]], most of [[nerve fibers]] decussate at [[optic chiasm]] and cause monocluar vision
** Monocular vision is manifested as [[strabismus]]
** Monocular vision is manifested as [[strabismus]]
** In [[albinism]],  [[macular]] pigment absent and [[fovea]] [[hypoplasia]] leads to decreased [[visual acuity]]
** In [[albinism]],  [[macular]] pigment is absent and [[fovea]] [[hypoplasia]] leads to decreased [[visual acuity]]
** [[Visual acuity]] ranges froHPS1 gene (HPS1), AP3B1 gene (HPS2), HPS3 gene (HPS3), HPS4 gene (HPS4), HPS5 gene (HPS5), HPS6 gene (HPS6), DTNBP1 gene (HPS7m 20/60 to 20/400 <ref name="pmid20301683"/><ref name="pmid31777350">{{cite journal| author=Marçon CR, Maia M| title=Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors. | journal=An Bras Dermatol | year= 2019 | volume= 94 | issue= 5 | pages= 503-520 | pmid=31777350 | doi=10.1016/j.abd.2019.09.023 | pmc=6857599 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31777350  }} </ref><ref name="pmid546241">{{cite journal| author=Witkop CJ| title=Albinism: hematologic-storage disease, susceptibility to skin cancer, and optic neuronal defects shared in all types of oculocutaneous and ocular albinism. | journal=Ala J Med Sci | year= 1979 | volume= 16 | issue= 4 | pages= 327-30 | pmid=546241 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=546241  }} </ref><ref name="pmid3288382">{{cite journal| author=King RA, Summers CG| title=Albinism. | journal=Dermatol Clin | year= 1988 | volume= 6 | issue= 2 | pages= 217-28 | pmid=3288382 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3288382  }} </ref>
** [[Visual acuity]] ranges from 20/60 to 20/400 <ref name="pmid20301683"/><ref name="pmid31777350">{{cite journal| author=Marçon CR, Maia M| title=Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors. | journal=An Bras Dermatol | year= 2019 | volume= 94 | issue= 5 | pages= 503-520 | pmid=31777350 | doi=10.1016/j.abd.2019.09.023 | pmc=6857599 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31777350  }} </ref><ref name="pmid546241">{{cite journal| author=Witkop CJ| title=Albinism: hematologic-storage disease, susceptibility to skin cancer, and optic neuronal defects shared in all types of oculocutaneous and ocular albinism. | journal=Ala J Med Sci | year= 1979 | volume= 16 | issue= 4 | pages= 327-30 | pmid=546241 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=546241  }} </ref><ref name="pmid3288382">{{cite journal| author=King RA, Summers CG| title=Albinism. | journal=Dermatol Clin | year= 1988 | volume= 6 | issue= 2 | pages= 217-28 | pmid=3288382 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3288382  }} </ref>


===Genetics===
==Genetics==
* [[Genetic mutation]] in [[albinism]] include:<ref name="pmid17980020">{{cite journal| author=Grønskov K, Ek J, Brondum-Nielsen K| title=Oculocutaneous albinism. | journal=Orphanet J Rare Dis | year= 2007 | volume= 2 | issue=  | pages= 43 | pmid=17980020 | doi=10.1186/1750-1172-2-43 | pmc=2211462 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17980020  }} </ref><ref> {{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK519018/ |title=Albinism - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref><ref name="pmid19390472">{{cite journal| author=Summers CG| title=Albinism: classification, clinical characteristics, and recent findings. | journal=Optom Vis Sci | year= 2009 | volume= 86 | issue= 6 | pages= 659-62 | pmid=19390472 | doi=10.1097/OPX.0b013e3181a5254c | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19390472  }} </ref>
* [[Genetic mutation]] in [[albinism]] include:<ref name="pmid17980020">{{cite journal| author=Grønskov K, Ek J, Brondum-Nielsen K| title=Oculocutaneous albinism. | journal=Orphanet J Rare Dis | year= 2007 | volume= 2 | issue=  | pages= 43 | pmid=17980020 | doi=10.1186/1750-1172-2-43 | pmc=2211462 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17980020  }} </ref><ref> {{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK519018/ |title=Albinism - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref><ref name="pmid19390472">{{cite journal| author=Summers CG| title=Albinism: classification, clinical characteristics, and recent findings. | journal=Optom Vis Sci | year= 2009 | volume= 86 | issue= 6 | pages= 659-62 | pmid=19390472 | doi=10.1097/OPX.0b013e3181a5254c | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19390472  }} </ref>
** [[Tyrosinase]] in [[OCA1]]; [[autosomal recessive]]
** [[Tyrosinase]] in OCA1; [[autosomal recessive]]
** P protein in [[OCA2]];[[autosomal recessive]]
** P protein in OCA2;[[autosomal recessive]]
** Tyrosinase-related protein 1 ([[TYRP1]])in [[OCA3]]; [[autosomal recessive]]
** Tyrosinase-related protein 1 ([[TYRP1]])in OCA3; [[autosomal recessive]]
** [[solute carrier family]] 45, member 2 ([[SLC45A2]]) in [[OCA4]]; [[autosomal recessive]]
** [[solute carrier family]] 45, member 2 ([[SLC45A2]]) in OCA4; [[autosomal recessive]]
** Gene mutation in [[OCA5]] is not identified; [[autosomal recessive]]
** Gene mutation in OCA5 is not identified; [[autosomal recessive]]
** [[SLC24A5]] in [[OCA]]6; [[autosomal recessive]]
** [[SLC24A5]] in OCA6; [[autosomal recessive]]
** Leucine-rich melanocyte differentiation associated protein ([[LRMDA]]) in [[OCA7]]; [[autosomal recessive]]
** Leucine-rich melanocyte differentiation associated protein ([[LRMDA]]) in OCA7; [[autosomal recessive]]
** Gene mutation in [[Hermansky-Pudlak syndrome]] ([[HPS]]) subtypes are as following:  
** [[Gene mutation]] in [[Hermansky-Pudlak syndrome]] ([[HPS]]) subtypes are as following:  
*** [[HPS1]], [[AP3B1]], [[HPS3]], [[HPS4]], [[HPS5]], [[HPS6]], [[DTNBP1]]; [[autosomal recessive]]
*** [[HPS1]], [[AP3B1]], [[HPS3]], [[HPS4]], [[HPS5]], [[HPS6]], [[DTNBP1]]; [[autosomal recessive]]
** [[LYST]] in [[Chediak-Higashi syndrome ]]; [[autosomal recessive]]
** [[LYST]] in [[Chediak-Higashi syndrome ]]; [[autosomal recessive]]
** [[GPR143]] in [[ocular albinism]] 1;[[ X-linked]]
** [[GPR143]] in [[ocular albinism]] 1 (OA1) ;[[ X-linked]]
 
== Associated Conditions==
* [[Hermansky-Pudlak syndrome]] ([[HPS]])
* [[Chediak-Higashi syndrome]] ([[CHS]])
* [[Angelman syndrome]] and [[Prader-Willi syndrome]]
 
==Microscopic Pathology==
* Macromelanosomes are seen in male patients with [[albinism]] and female carriers of OA1 <ref name="pmidhttps://doi.org/10.1167/iovs.05-0834">{{cite journal| author=Schmoldt A, Benthe HF, Haberland G| title=Digitoxin metabolism by rat liver microsomes. | journal=Biochem Pharmacol | year= 1975 | volume= 24 | issue= 17 | pages= 1639-41 | pmid=https://doi.org/10.1167/iovs.05-0834 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10  }} </ref>


==References==
==References==

Latest revision as of 14:47, 16 September 2021

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]

Overview

Melanocytes are derived from neural crest ectoderm and are found in hair follicles, skin, eyes, and inner ear. Melanocytes produce melanin which protects skin from ultraviolet. Tyrosinase converts tyrosine to DOPA, dopaquinone, and then melanin. Mutation in Tyrosinase enzyme is responsible for causing albinism. Additionally, melanin is responsible for development of the fovea, optic nerves, optic tracts, and visual cortex.Decussation of some optic nerve fibers at optic chiasm are essential for binocular vision. However, in albinism, most of nerve fibers decussate at optic chiasm and cause monocluar vision presented as strabismus. In ocular albinism, macular pigment is absent and fovea hypoplasia leads to decreased visual acuity.

Pathophysiology

Physiology

Pathogenesis

Genetics

Associated Conditions

Microscopic Pathology

  • Macromelanosomes are seen in male patients with albinism and female carriers of OA1 [9]

References

  1. "Albinism - StatPearls - NCBI Bookshelf".
  2. 2.0 2.1 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G; et al. (1993). "GeneReviews®". PMID 20301683.
  3. Marçon CR, Maia M (2019). "Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors". An Bras Dermatol. 94 (5): 503–520. doi:10.1016/j.abd.2019.09.023. PMC 6857599 Check |pmc= value (help). PMID 31777350.
  4. Witkop CJ (1979). "Albinism: hematologic-storage disease, susceptibility to skin cancer, and optic neuronal defects shared in all types of oculocutaneous and ocular albinism". Ala J Med Sci. 16 (4): 327–30. PMID 546241.
  5. King RA, Summers CG (1988). "Albinism". Dermatol Clin. 6 (2): 217–28. PMID 3288382.
  6. Grønskov K, Ek J, Brondum-Nielsen K (2007). "Oculocutaneous albinism". Orphanet J Rare Dis. 2: 43. doi:10.1186/1750-1172-2-43. PMC 2211462. PMID 17980020.
  7. "Albinism - StatPearls - NCBI Bookshelf".
  8. Summers CG (2009). "Albinism: classification, clinical characteristics, and recent findings". Optom Vis Sci. 86 (6): 659–62. doi:10.1097/OPX.0b013e3181a5254c. PMID 19390472.
  9. Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID https://doi.org/10.1167/iovs.05-0834 Check |pmid= value (help).

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