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==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]].


== Causes ==
==Pathophysiology==
Albinism is a [[genetic disorder]]; it is not an infectious disease and cannot be transmitted through contact, blood transfusions, etc.  The principal gene which results in albinism prevents the body from making the usual amounts of the [[biological pigment|pigment]] [[melanin]]. Most forms of albinism are the result of the [[biological inheritance]] of [[dominance relationship|genetically recessive]] [[allele]]s ([[gene]]s) passed from both parents of an individual, though some rare forms are inherited from only one parent. There are other [[genetic mutation]]s which are proven to be associated with albinism. All alterations, however, lead to changes in melanin production in the body.<ref name="eMedicine1">[http://www.emedicine.com/derm/topic12.htm "Albinism"], by Dr. Raymond E. Boissy, Dr. James J. Nordlund, et al., at [[eMedicine]], [[22 August]] [[2005]]; retrieved [[31 March]] [[2007]]</ref><ref name="OMIM1">[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=omim&term=albinism Online ''Mendelian Inheritance in Man'' Database], at [[Johns Hopkins University]] (see also [[Mendelian Inheritance in Man]] for more information about this source).</ref>  
===Physiology===
* [[Melanocytes]] are derived from [[neural crest]] [[ectoderm]] and are found in [[hair follicles]], [[skin]], [[eyes]], and [[inner ear]]
* [[Melanocytes]] account for 5% to 10% of cells in [[epidermal]] [[basal layers]]
* [[Melanocytes]] contain [[melanosomes]] which produce [[melanin]]
* [[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
* [[Melanin]] converts 2 forms named [[eumelanin]] and [[pheomelanin]]
* [[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]]
* On [[melanocytes]], activation of [[melanocortin one receptors]] ([[MC1R]]) lead to synthesis of [[eumelanin]] over [[pheomelanin]] <ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/books/NBK519018/ |title=Albinism - StatPearls - NCBI Bookshelf |format= |work= |accessdate=}}</ref><ref name="pmid20301683">{{cite journal| author=Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G | display-authors=etal| title=GeneReviews® | journal= | year= 1993 | volume=  | issue=  | pages=  | pmid=20301683 | doi= | pmc= | url= }} </ref>


Albinism used to be categorized as [[tyrosinase]]-positive or -negative. In cases of tyrosinase-positive albinism, the [[enzyme]] tyrosinase is present. The [[melanocyte]]s (pigment cells) are unable to produce melanin for any one of a variety of reasons that do not directly involve the tyrosinase enzyme. In tyrosinase negative cases, either the tyrosinase enzyme is not produced or a nonfunctional version is produced. This classification has been rendered obsolete by recent research.<ref name="Facts_Albinism"> [http://albinism.med.umn.edu/facts.htm "Facts about Albinism"], by Richard King ''et al''. </ref>
===Pathogenesis===
*  [[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]] 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]]
* [[Ocular]] [[albinism]] pathway:
** 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
** 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
** Monocular vision is manifested as [[strabismus]]
** In [[albinism]],  [[macular]] pigment is absent and [[fovea]] [[hypoplasia]] leads to decreased [[visual acuity]]
** [[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>


The chance of offspring with albinism resulting from the pairing of an organism with albinism and one without albinism is low, as discussed in more detail below. However, because organisms can be carriers of genes for albinism without exhibiting any traits, albinistic offspring can be produced by two non-albinistic parents. Albinism usually occurs with equal frequency in both genders.<ref name="eMedicine1" /> An exception to this is ocular albinism, because it is passed on to offspring through X-linked inheritance. Thus, males more frequently have ocular albinism.<ref name="Facts_Albinism"> [http://albinism.med.umn.edu/facts.htm "Facts about Albinism"], by Richard King ''et al''. </ref>
==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>
** [[Tyrosinase]] in OCA1; [[autosomal recessive]]
** P protein in OCA2;[[autosomal recessive]]
** Tyrosinase-related protein 1 ([[TYRP1]])in OCA3; [[autosomal recessive]]
** [[solute carrier family]] 45, member 2 ([[SLC45A2]]) in OCA4; [[autosomal recessive]]
** Gene mutation in OCA5 is not identified; [[autosomal recessive]]
** [[SLC24A5]] in OCA6; [[autosomal recessive]]
** Leucine-rich melanocyte differentiation associated protein ([[LRMDA]]) in OCA7; [[autosomal recessive]]
** [[Gene mutation]] in [[Hermansky-Pudlak syndrome]] ([[HPS]]) subtypes are as following:
*** [[HPS1]], [[AP3B1]], [[HPS3]], [[HPS4]], [[HPS5]], [[HPS6]], [[DTNBP1]]; [[autosomal recessive]]
** [[LYST]] in [[Chediak-Higashi syndrome ]]; [[autosomal recessive]]
** [[GPR143]] in [[ocular albinism]] 1 (OA1) ;[[ X-linked]]


Because organisms with albinism have skin that lacks (sufficiently or entirely) the dark pigment melanin, which helps protect the skin from [[ultraviolet]] [[radiation]] coming from the sun, they can [[sunburn]] easily from overexposure. (See [[human skin color]] for more information). Lack of melanin in the eye also results in problems with vision, related and unrelated to [[photosensitivity]], which are discussed further below.
== Associated Conditions==
* [[Hermansky-Pudlak syndrome]] ([[HPS]])
* [[Chediak-Higashi syndrome]] ([[CHS]])
* [[Angelman syndrome]] and [[Prader-Willi syndrome]]


Most humans and many animals with albinism appear white or very pale; the multiple types of melanin pigment are responsible for brown, black, gray, and some yellow colorations. In some animals, especially albinistic birds and reptiles, ruddy and yellow hues or other colors may be present on the entire body or in patches (as is common among pigeons), due to the presence of other pigments unaffected by albinism such as [[porphyrin]]s, [[pteridine]]s and psittacins, as well as [[carotenoid]] pigements derived from the diet. Some animals are white or pale due to [[chromatophore]] (pigment cell) defects, do not lack melanin ''production'', and have normal eyes; they are referred to as [[leucism|leucistic]]. The direct opposite of albinism, an unusually high level of melanin pigmentation (and sometimes absence of other types of pigment in species that have more than one), is known as [[melanism]], and results in an appearance darker than non-melanistic specimens from the same genepool.<ref name="Feinstein">[http://www.birdersworld.com/brd/default.aspx?c=a&id=676 "Feather Colors: What We See"] by Dr. Julie Feinstein of the American Museum of Natural History (NY), in ''Birder's World Magazine'' online archive; sourced December 2006, actual authoring/publication date unspecified.</ref> Albinism-like conditions may affect other pigments or pigment-production mechanisms in some animals (e.g. "whiteface", a lack of psittacins that can affect some parrot species.).<ref name="Hesford">[http://www.birdhobbyist.com/parrotcolour/parblu04.html "The Parblue Puzzle: Part 4 &mdash; Common Parblue Varieties: The Cockatiel &#91;''Nymphicus hollandicus''&#93;"] by Clive Hesford, ''The Genetics of Colour in the Budgerigar and Other Parrots'', January 1998</ref> Another is common in reptiles and amphibians: axanthism, in which [[xanthophore]] [[metabolism]], instead of [[Synthesis#Chemical synthesis|synthesis]] of melanin, is affected, resuling in reduction or absence of red and yellow pteridine pigments.<ref name="ABPC">[http://www.livingunderworld.org/biology/caudata/ "Amphibian Biology & Physiology: ''Caudata''"] at ''Amphibian Information Resource: An Educational Web Project About Amphibian Species''; sourced December 2006, actual authoring/publication date unspecified.</ref> Of all these conditions, only albinism and melanism affect humans.
==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>
[[Image:Wistar_rat.jpg|thumb|left|px280|An albino [[Wistar rat]], a strain commonly used for both [[animal testing|biomedical and basic research.]]]]
The eyes of an animal with albinism occasionally appear red due to the underlying retinal blood vessels showing through where there is not enough pigment to cover them. In humans this is rarely the case, as a human eye is quite large and thus produces enough pigment to lend opacity to the eye, often colouring the iris pale blue. However, there are cases in which the eyes of an albinistic person appear red or purple, depending on the amount of pigment present.
The albinistic are generally (but see related disorders below) as healthy as the rest of their species, with growth and development occurring as normal, and albinism by itself does not cause mortality<ref name="eMedicine1" /> (though the lack of pigment is an elevated risk for skin cancer and other problems.) Many animals with albinism lack their protective camouflage and are unable to conceal themselves from their predators or prey; the survival rate of animals with albinism in the wild is usually quite low. <ref name="survival1">Ilo Hiler, Albinos. ''Young Naturalist''. The Louise Lindsey Merrick Texas Environment Series, No. 6, pp. 28-31. Texas A&M University Press, College Station (1983)</ref> <ref name="survival2"> S. Dobosz, K. Kohlmann, K. Goryczko, H. Kuzminski (2000) Growth and vitality in yellow forms of rainbow trout. ''Journal of Applied Ichthyology.'' 16, 117–120.</ref> However the novelty of albino animals has occasionally led to their protection by groups such as the [[Albino Squirrel Preservation Society]]. 


Intentionally-bred albinistic strains of some animal species are commonly used as [[model organism]]s in biomedical study and experimentation. Examples include the [[BALB/c]] mouse and Wistar and Sprague Dawley rat strains, while albino rabbits were historically used for [[Draize test|Draize toxicity testing]]. <ref name="Draize">Draize, J.H., Woodard, G. & Calvery, H.O. (1944) Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. ''J. Pharmacol. and Exp. Therapeutics.'' 82, 377–390.</ref>  Albino axolotls, zebrafish, medaka and frogs are other common laboratory animals.
==References==
 
{{Reflist|2}}
The incidence of albinism can be artificially increased in
fish by exposing the eggs to [[heavy metals]].<ref>{{cite journal|url=http://www.ufrgs.br/ni/vol3num1%5CBrito%20&%20Caramaschi.pdf|title=An albino armored catfish ''Schizolecis guntheri'' (Siluriformes: Loricariidae) from an Atlantic Forest coastal basin|first=Marcelo F. G.|last=de Brito|coauthors=Caramaschi, Érica P.|journal=Neotropical Ichthyology|volume=3|issue=1|pages=123-125|pages=2005|format=[[PDF]]}}</ref>


==References==
[[Category:Endocrinology]]
[[Category:Dermatology]]
[[Category:Needs overview]]


{{Reflist|2}}
{{WS}}
{{WH}}

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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