Albinism

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

Albinism is an inherited disease that is caused by a genetic mutation. This mutation impairs melanin synthesis; therefore, the number of melanocytes is preserved. The different types of albinism include, Oculocutaneous albinism(OCA), Hermansky-Pudlak syndrome (HPS),Chediak-Higashi syndrome (CHS), and Ocular albinism (OA). Patients may present cutaneous and ocular findings. Cutaneous features include hypopigmented/ white hair, skin, and eyelashes. Ocular features include photophobia, decreased visual acuity, pink eyes, and hypopigmentation of iris, refractive errors, strabismus, nystagmus, foveal hypoplasia, and iris transillumination. The management of cutaneous and ocular manifestations of albinism include avoidance of prolonged sun exposure, periodic dermatologist evaluation for skin cancer, corrective lenses for refractive errors, tinted lenses/glasses for photophobia, bifocal or low-vision aids in older children, eye-patching in infants for reduction of strabismus, contact lenses or eye surgery in presence of nystagmus. Additionally, nitisinone can be used to improve pigmentation in OCA1.

Albinism was first discovered in 1908 by a British physician named Sir Archibald Edward Garrod. At first, it was believed that albinism is caused by a lack of melanocytes. In late 1950, it was proved that albinism is caused by tyrosine kinase inactivity.

Albinism is classified based on genetic mutation. The different types of albinism include Oculocutaneous albinism(OCA), Hermansky-Pudlak syndrome (HPS),Chediak-Higashi syndrome (CHS), and Ocular albinism (OA).

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.

Albinism is caused by genetic mutations that impair melanin synthesis. The number of melanocytes is preserved.

Oculocutaneous albinism and ocular albinism must be differentiated from the following rare disease: Hermansky-Pudlak syndrome, Chediak-Higashi syndrome, Griscelli syndrome, Waardenburg syndrome type II, Vici syndrome, Tietz albinism-deafness syndrome, Angelman syndrome, Prader-Willi syndrome, Cross-McKusick-Breen syndrome, Achromatopsia, Aland Island eye disease (Forsius-Eriksson syndrome), Aniridia, and Congenital nystagmus.

The prevalence of albinism is estimated to be 1:17,000 to 1: 20,000 in the general population.The Prevalence of different types of albinism varies and the most prevalent form is Oculocutaneous albinism 2 (OCA2).

Albinism is inherited due to genetic mutations. Individuals with positive familial history are at risk of having albinism.

There is no screening test for albinism.Individuals with familial history of albinism can undergo genetic sequence analysis.

The complications of albinism include skin cancer, sunburn, decreased visual acuity, poor self-image and self-isolation lead to depression. Patients with albinism has a normal life expectancy and do not have developmental delay or mental retardation.

Patients may present both cutaneous and ocular findings. Cutaneous features include hypopigmented/ white hair, skin, and eyelashes. Ocular features include photophobia, decreased visual acuity, pink eyes, and hypopigmentation of iris.

Ocular physical examination findings include refractive errors, strabismus, nystagmus, foveal hypoplasia, iris transillumination, decreased iris pigmentation. Cutaneous finding varies from white to hypopigmented or light brown skin, hair, eyebrow, and eyelashes.

The laboratory tests for diagnosis of albinism include hair bulb assay for determination of tyrosinase activity, Genetic sequence testing which is the most definite test, bleeding tests in suspected patients with Hermansky-Pudlak syndrome, and evaluation of polymorphonuclear leukocyte function in suspected patients with Chediak-Higashi syndrome.

There are no electrocardiogram findings associated with albinism.

There are no x-ray findings associated with albinism.

There are no CT findings associated with albinism.

There are no MRI findings associated with albinism.

There are no echocardiography or ultrasound findings associated with albinism.

Macular optical coherence tomography can be used in young patients with nystagmus and foveal abnormalities to determine the cause.

Ophthalmology examination and evaluation should be done to confirm the diagnosis. Visual-evoked potential testis used for recognition acuity in children and shows misrouting of optic nerves.

The management of cutaneous and ocular manifestations of albinism include avoidance of prolonged sun exposure, periodic dermatologist evaluation for skin cancer, corrective lenses for refractive errors, tinted lenses/glasses for photophobia, bifocal or low-vision aids in older children, eye-patching in infants for reduction of strabismus, contact lenses or eye surgery in presence of nystagmus. Additionally, nitisinone can be used to improve pigmentation in OCA1.

Eye muscles surgery can improve ocular alignment and vision in patients with severe ocular features. However, it may not be really helpful in strabismus improvement due to lack of necessary ocular connections.

Genetic consultation is recommended for couples diagnosed with albinism, familial history of albinism or parents of albino child who consider having future pregnancy.

There is no secondary prevention for albinism.

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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]

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Albinism was first discovered in 1908 by a British physician named Sir Archibald Edward Garrod. At first, it was believed that albinism is caused by a lack of melanocytes. In late 1950, it was proved that albinism is caused by tyrosine kinase inactivity.

• The discovery of albinism occured as the following: ^{[1] [2] [3]}
• Albinism, from the Latin Albu, means white
• In 1908, a British physician named Sir Archibald Edward Garrod discovered Albinism
• Sir Archibald Edward Garrod stated that albinism is caused by failure of an intercellular activity
• In late 1950, it was proved that albinism is caused by tyrosine kinase inactivity, not due to lack of melanocytes
• Between 1920-1935, British physiologist H.S.Raper did studies on melanogenesis
• In 1966, Snowflack was the first case of albino gorilla which was discovered

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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]

Albinism is classified based on genetic mutation. The different types of albinism include, Oculocutaneous albinism(OCA), Hermansky-Pudlak syndrome (HPS),Chediak-Higashi syndrome (CHS), and Ocular albinism (OA).

• Albinism is classified based on genetic mutation^[1][2]
• The different types and subtypes include:
  • Oculocutaneous albinism(OCA); 4 subtypes
  • Hermansky-Pudlak syndrome (HPS); 8 subtypes
  • Chediak-Higashi syndrome (CHS); 1 type
  • Ocular albinism (OA); 2 types

Albinism Types

Type	Gene Position	Affected Protein
OCA1	11q14-21	Tyrosinase
OCA2	15q11-13	P-protein
OCA3	9p23	Tyrosinase-related protein
OCA4	5p	SLC45A2
HPS1	10q23.1-q23.3	HPS1
HPS2	5q14.1	AP3B1
HPS3	3q24	HPS3
HPS4	22q11.2-q12.2	HPS4
HPS5	11p15-p13	HPS5
HPS6	10q24.3	HPS6
HPS7	6p22.3	Dysbindin protein
HPS8	19q13	BLOC1S3
CHS	1q42.1-q42.2	Lysosomal trafficking regulator
OA (X-linked recessive)	Xp22.3	GPR143
AROA( autosomal recessive)	Not a distinct position	Tyrosinase in some cases;P protein in some cases

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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]

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.

• 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]

• 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]

• 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:
    • HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1; autosomal recessive
  • LYST in Chediak-Higashi syndrome ; autosomal recessive
  • GPR143 in ocular albinism 1 (OA1) ;X-linked

• Hermansky-Pudlak syndrome (HPS)
• Chediak-Higashi syndrome (CHS)
• Angelman syndrome and Prader-Willi syndrome

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

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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]

Albinism is caused by genetic mutations that impair melanin synthesis. The number of melanocytes is preserved.

• Albinism is caused by genetic mutations that impair melanin synthesis ^[1]
• Genetic mutations that lead to different subtypes of albinism are mentioned in both classification and pathophysiology sections
• The number of melanocytes is preserved ^[2]

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There are some diseases that may present similarly to albinism, and need to be differentiated from albinism. These diseases are; Chediak-Higashi syndrome,Tuberous sclerosis and Waardenburg syndrome

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

The prevalence of albinism is estimated to be 1:17,000 to 1:20,000 in the general population.The Prevalence of different types of albinism varies and the most prevalent form is Oculocutaneous albinism 2 (OCA2).

• The prevalence of albinism is estimated to be 1:17,000 to 1:20,000 in the general population ^{[1] [2][3]}
• In the US, about 18,000 people have albinism
• The Prevalence of different types of albinism varies
• Oculocutaneous albinism 2 (OCA2) is the most prevalent form
• The prevalence of different subtypes are as follows: ^[4]
  • OCA1 occurs in 1: 40,000 individuals worldwide; 70% of cases occurs in America and China
  • OCA2 occurs in 1: 39,000 individuals worldwide; this prevalence is estimated to be 1: 10,000 in African Americans, 1:36,000 in overall Americans, and 1:3,900 in Sub-Saharan Africa
  • OCA3 occurs in 1: 8500 individuals in Africa
  • OCA4 occurs in 1: 100,000 individuals; accounts for 24% of Japanese albinism
  • OCA5, OCA6, and OCA7 cases are very rare
  • Hermansky-Pudlak syndrome (HPS) occurs in 1: 500,000 population worldwide; the prevalence of HPS is 1:1800 in Puerto Rico
  • Chediak-Higashi syndrome (CHS) is very rare; less than 50 cases were identified in the last 20 years
  • Ocular albinism (OA1) occurs in 1:50,000 individuals

• As albinism is a hereditary disease, it can be diagnosed from early ages of life

• There is no racial predilection to albinism

• Since ocular albinism is considered a X-linked recessive, it affects man more than women

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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]

Albinism is inherited due to genetic mutations. Individuals with positive familial history are at risk of having albinism.

• Albinism is inherited due to genetic mutations ^[1]
• Individuals with positive familial history are at risk of having albinism

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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]

There is insufficient evidence to recommend routine screening for albinism. Individuals with familial history of albinism can undergo genetic sequence analysis.

• There is insufficient evidence to recommend routine screening for albinism ^[1]
• Individuals with familial history of albinism can undergo genetic sequence analysis

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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]

The complications of albinism include skin cancer, sunburn, decreased visual acuity, poor self-image and self-isolation lead to depression. Patients with albinism has a normal life expectancy and do not have developmental delay or mental retardation.

• The complications of albinism are as follows:^[1][2][3]
  • Skin cancer including basal cell carcinoma and squamous cell carcinoma
    • 80% of skin cancer are diagnosed in patients aged over 55 years ^[4][5]
  • Sunburn
  • Decreased visual acuity
  • Poor self-image and self-isolation that may lead to depression
  • Individuals with albinism are at increased risk of attention deficit disorder
  • Bleeding disorders in patients with Hermansky-Pudlak syndrome
  • Infection risk in Chediak-Higashi syndrome

• Patients with albinism has a normal life expectancy
• Albinism does not cause developmental delay or mental retardation
• Patients may have delayed visual maturation ^[6]Closing </ref> missing for <ref> tag

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