Albinism pathophysiology: Difference between revisions

Jump to navigation Jump to search
No edit summary
 
(32 intermediate revisions by 4 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{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]].


Please help WikiDoc by adding content hereIt's easy! Click [[Help:How_to_Edit_a_Page|here]]  to learn about editing.
==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}}


{{Reflist|2}}
[[Category:Endocrinology]]
[[Category:Dermatology]]
[[Category:Needs overview]]


[[Category:Needs content]]
{{WS}}
{{WH}}

Latest revision as of 14:47, 16 September 2021

Albinism Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Albinism from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Albinism pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Albinism pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Albinism pathophysiology

CDC on Albinism pathophysiology

Albinism pathophysiology in the news

Blogs on Albinism pathophysiology

Directions to Hospitals Treating Albinism

Risk calculators and risk factors for Albinism pathophysiology

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).

Template:WS Template:WH