Albinism pathophysiology: Difference between revisions
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{{Albinism}} | {{Albinism}} | ||
{{CMG}}; {{AE}} {{S.M}} | |||
==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=== | |||
* [[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> | |||
===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> | |||
==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]] | |||
== 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== | ||
{{Reflist|2}} | |||
[[Category:Endocrinology]] | |||
[[Category:Dermatology]] | |||
[[Category:Needs overview]] | |||
{{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
- 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 skin
- On melanocytes, activation of melanocortin one receptors (MC1R) lead to synthesis of eumelanin over pheomelanin [1][2]
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 [2][3][4][5]
Genetics
- Genetic mutation in albinism include:[6][7][8]
- 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:
- LYST in Chediak-Higashi syndrome ; autosomal recessive
- 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
References
- ↑ "Albinism - StatPearls - NCBI Bookshelf".
- ↑ 2.0 2.1 Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G; et al. (1993). "GeneReviews®". PMID 20301683.
- ↑ 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. - ↑ 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.
- ↑ King RA, Summers CG (1988). "Albinism". Dermatol Clin. 6 (2): 217–28. PMID 3288382.
- ↑ 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.
- ↑ "Albinism - StatPearls - NCBI Bookshelf".
- ↑ Summers CG (2009). "Albinism: classification, clinical characteristics, and recent findings". Optom Vis Sci. 86 (6): 659–62. doi:10.1097/OPX.0b013e3181a5254c. PMID 19390472.
- ↑ 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).