Albinism oculocutaneous

December 31, 2014

Synonyms

Overview

Albinism:

Albinism is caused by a mutation in one of several genes. Each of these genes provides instructions for making one of several proteins involved in the production of melanin. Melanin is produced by cells called melanocytes, which are found in your skin and eyes. A mutation may result in no melanin at all or a significant decline in the amount of melanin. In some types of albinism, a person must inherit two copies of a mutated gene — one from each parent — in order to have albinism (recessive inheritance). Regardless of which gene mutation is present, vision impairment is a key feature of all types of albinism. These impairments are caused by irregular development of the optic nerve pathways from the eye to the brain and from abnormal development of the retina.

Oculocutaneous albinism:

Oculocutaneous albinism is a group of rare inherited disorders characterized by a reduction or complete lack of melanin pigment in the skin (cutaneous), hair and eyes (oculo) as well as reduces pigmentation of the colored part of the eye (the iris) and the light-sensitive tissue at the back of the eye (the retina). Individuals affected by oculocutaneous albinism have very light skin and light-colored irises.

They may also have vision problems such as decreased sharpness of vision, rapid eye movements (nystagmus), crossed eyes (strabismus), or increased sensitivity to light (photophobia). Other changes include foveal hypoplasia (which affects visual acuity) and mis-routing of the optic nerves. All individuals with OCA have the above visual changes but the amount of skin, hair and iris pigment can vary depending on the gene (or type of OCA) and mutation involved. Long-term sun exposure greatly increases the risk of skin damage and skin cancers, including an aggressive form of skin cancer called melanoma, in people with this condition.

Overall, an estimated 1 in 20,000 people worldwide are born with OCA. OCA is caused by mutations in several genes that control the synthesis of melanin within the melanocytes. All types of OCA are caused by gene mutations that are inherited in an autosomal recessive manner. Researchers have identified multiple types of oculocutaneous albinism, which are distinguished by their specific skin, hair, and eye color changes and by their genetic cause.

Subdivisions of Oculocutaneous Albinism:

There are seven types of OCA (OCA1-7) caused by mutations in seven different genes. Oculocutaneous albinism is inherited as an autosomal recessive genetic condition.

Oculocutaneous albinism type 1 (OCA1) is associated with reduced production of melanin in the skin, hair and eyes. There are two types of OCA1. Individuals affected with OCA1A have a complete absence of melanin pigment resulting in white hair and white skin at birth and irises that do not become darker over time. Visual acuity in individuals can range from 20/200 to 20/400. Individuals with OCA1B have white or light yellow hair at birth that can darken over time, white skin that darkens over time and irises that may change from light blue to green or brown over time. Vision is usually better in individuals with OCA1B than in those with OCA1A. OCA1 is associated with abnormalities (mutations) in the tyrosinase (TYR) gene. The TYR gene is responsible for the production of the enzyme tyrosinase which is the key enzyme in the formation of melanin pigment. Some TYR mutations result in the production of a completely nonfunctioning tyrosinase enzyme and no melanin pigment is formed. This results in OCA1A. Different TYR mutations result in the production of a tyrosinase enzyme with limited enzymatic activity but it is still able to produce small amounts of melanin pigment. This type of OCA1 is called OCA1B. In the case of OCA1B, melanin pigment will accumulate with time in the skin, hair and eyes.

Oculocutaneous albinism type 2 (OCA2) is associated with the same vision problems that occur in OCA1. Individuals with OCA2 have a wide range of skin pigmentation that is partially dependent on their genetic background of the affected individual and the mutations present. Hair color is usually not completely white and there can be some pigment present in the skin but skin color is usually lighter than in unaffected relatives. Individuals with extensive sun exposure can develop pigmented nevi and lentigines (dark spots on the skin). This does not occur with other types of OCA. A reduction in skin pigment is apparent in Africans and African-Americans but skin coloration appears close to normal in other populations with normally lighter skin pigmentation but affected individuals do not tan. Brown OCA is a type of OCA2 where hair and skin coloration is darker. This type of OCA2 has only been reported in individuals with African ancestry. OCA2 is associated with mutations in the OCA2 gene (also called the P gene). The OCA2 gene is responsible for production of the OCA2 protein. The precise function of the OCA2 protein is unknown, but it is thought to be important in regulating the movement of the substrate tyrosine into the melanosome as well as regulating the internal environment of the melanosome.

Oculocutaneous albinism type 3 (OCA3) was initially described in the African population. Affected individuals have red to reddish-brown skin, ginger or reddish hair, and hazel or brown eyes and the condition was initially termed rufous albinism. OCA3 has now been identified in several additional populations including those of Asian descent (Chinese and Japanese), Asian Indian and Northern European. Affected individuals of Asian heritage can have blond hair with light brown eyebrows with skin lighter than their parents. Both hair and skin pigmentation increases with age. Reduction in visual acuity is not as severe as in OCA1 or OCA2. Nystagmus and photophobia may not be present. OCA3 is associated with mutations in the tyrosinase related protein 1 (TYRP1) gene. This gene is responsible for the production of tyrosinase-related protein-1, an enzyme like tyrosinase, which is involved in the production of melanin. The TYRP1 enzyme is part of a gene family that includes tyrosinase and the tyrosinase related protein-2 (TYRP2), all of which are enzymes involved in melanin biosynthesis. The TYRP1 enzyme is responsible for later steps (after the initial tyrosinase step) in melanin pigment production.

Oculocutaneous albinism type 4 (OCA4) is characterized by physical features that are similar to those of OCA2. Hair color of affected individuals can range from yellow to brown. Visual acuity can range from 20/30 to 20/400 depending on the amount of pigment that is present, but acuity is usually in the range of 20/100 to 20/200. OCA4 was initially identified in an individual of Turkish origin and has been also found in Asian populations including Japanese and Korean and German individuals. OCA4 is associated with mutations in the SLC45A2 gene (also called the membrane-associated transporter protein; MATP). The SLC45A2 gene is responsible for the production of a membrane associated transporter protein formed with 12 transmembrane helices. The precise function of this protein is unknown but it is required for the normal production of melanin by the melanocyte.

Oculocutaneous albinism type 5 (OCA5) has been found in only one family in Pakistan. Affected individuals have golden colored hair, white skin and the same visual problems that occur in OCA1. Visual acuity in this family was 6/60. The gene responsible for OCA5 has been located on chromosome 4 (4q24). 14 genes are in this location, but the specific causative gene for OCA5 has not yet been determined.

Oculocutaneous albinism type 6 (OCA6) is characterized as having golden to light to dark brown hair, white skin and brownish irides and has been classified as autosomal recessive ocular albinism (AROA), though individuals are hypopigmented when compared to their parents. Only a few individuals have been identified with this type of albinism and all of the clinical features of OCA6 have not been determined but it is assumed that the reduction in visual acuity will not be as severe as seen in OCA1. OCA6 is associated with mutations in the SLC24A5 gene. The SLC24A5 gene is responsible for the production of a membrane associated transporter protein. The precise function of this protein is unknown but it belongs to a family of potassium-dependent sodium/calcium exchangers. It may be involved in the maturation of melanosomes.

Oculocutaneous albinism type 7 (OCA7) is characterized with blond to dark brown hair and skin which is more hypopigmented than parents. Individuals had nystagmus and iris transillumination. Visual acuity ranges from 6/18 to 3/60. OCA7 is associated with mutations in C10orf11. The isoform 1 open reading frame encodes a 226 amino acid protein containing a leucine-rich repeat. The function of the protein is unknown but is thought to play a role in melanocyte differentiation.

Symptoms

Cutaneous photosensitivity
Generalized hypopigmentation
Hypopigmentation of hair
Nystagmus
Ocular albinism
Visual impairment
Photophobia
Freckling
Strabismus
Several vision problems
Reduced iris pigment (iris transillumination)
Reduced retinal pigment,
Macular hypoplasia
Poor visual acuity
Reduces depth perception

Causes

Melanin pigment is the major pigment responsible for coloration of skin, hair and eyes. There are two types of melanin pigment, brown-black eumelanin and yellow-red pheomelanin. All melanin pigment is a combination of these two types of pigment. Melanin pigment is produced in specialized cells called melanocytes. Mutations in genes responsible for the proteins that are necessary for the melanocyte to make melanin pigment result in a reduction or absence of melanin pigment in the skin, hair and eyes of the affected individual and this condition is termed oculocutaneous albinism (OCA). OCA is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits an abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Seven genes have been identified that are associated with different types of OCA. Each of these genes is important in the production of melanin pigment that takes place in cells called melanocytes that are located in the skin, hair follicle, iris and retina of the eye. In the case of skin and hair pigmentation, the melanocyte transfers the melanin pigment to the keratinocyte, the cell that is responsible for skin and hair. Pigment in the eye is produced in the iris and in the retinal pigment epithelium.

Prevention

Skin care in individuals with OCA1 is dictated by the amount of pigment in the skin and the cutaneous response to sunlight

Diagnosis

Physical exam
Description of changes in pigmentation
Thorough exam of the eyes
Comparison of your child's pigmentation to that of other family members
DNA sequencing of the seven responsible genes is required to accurately determine which type of OCA is present

Treatment

Albinism is a genetic disorder, treatment is limited. But getting proper eye care and monitoring skin for signs of abnormalities are especially important.

Treatment includes covering the skin from sun exposure by using sunscreen and protective clothing and attending to vision problems by wearing glasses.