Information on the following diseases can be found in the Related Disorders section of this report:

• Hermansky-Pudlak syndrome
• ocular albinism
• congenital motor nystagmus

Oculocutaneous albinism type 1 (OCA1) is associated with reduced production of melanin in the skin, hair and eyes. Several vision problems can occur with this condition including an involuntary movement of eyes back and forth (nystagmus), reduced iris pigment, reduced retinal pigment, lack of development of the fovea (foveal hypoplasia) leading to photophobia, poor visual acuity, and abnormal connections in the nerves from the retina to the brain that prevents the eyes from tracking together and reduces depth perception. Individuals affected with OCA1A have white hair and white skin at birth and irises that do not become darker over time. Individuals with OCA1B have white or light yellow hair at birth that darkens over time, white skin that darkens over time and irises that may change to green or brown over time. Vision is usually better in those with OCA1B than in those with OCA1A. OCA1 is associated with mutations in the TYR gene that encodes the enzyme tyrosinase.

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 genetic background. Hair color is usually not completely white. There is usually some pigment present but skin color is usually lighter than in unaffected relatives. Brown OCA is a type of OCA2 in which a reduced skin pigment is apparent in Africans and African-Americans but pigment appears close to normal in other populations. OCA2 is associated with mutations in the OCA2 gene, formerly called the P gene.

Oculocutaneous albinism type 3 has only been described in the African population and includes red to reddish-brown skin, ginger or reddish hair and hazel or brown eyes. Vision problems are consistent with other types of OCA except that the optic nerves do not seem to be affected. OCA3 is associated with mutations in the TYRP1 gene.

Oculocutaneous albinism type 4 is characterized by physical features that are identical to those of OCA2. OCA4 is associated with mutations in the SLC45A2 gene (formerly called MATP).

Oculocutaneous albinism is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits the same 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.

Four genes have been identified that are associated with OCA. Each of these genes is important in the production of melanin that takes place in cells called melanocytes that are located in the skin, hair follicle and iris and retina of the eye.
OCA1 is associated with abnormalities (mutations) in the TYR gene. The TYR gene is responsible for the production of the tyrosinase enzyme that is necessary for the formation of melanin pigment. Some TYR mutations result in the production of a nonfunctioning tyrosinase enzyme and no melanin pigment is formed. This type of OCA1 is called OCA type 1A. Other TYR mutations result in the production of a tyrosinase enzyme with reduced function so that a reduced amount of melanin pigment is formed. This type of OCA1 is called OCA type 1B.

OCA2 is associated with mutations in the OCA2 gene (also called the P gene). The OCA2 gene is responsible for production of the P protein. The precise function of the P protein is unknown, but it is required for the normal production of melanin.

OCA3 is associated with mutations in the TYRP1 gene. This gene is responsible for the production of tyrosinase-related protein. This condition has been described in the African American population only.

OCA4 is associated with mutations in the SLC45A2 gene (also called the MATP). The SLC45A2 gene is responsible for the production of this membrane associated transporter protein. The precise function of this protein is unknown but it is required for the normal production of melanin.

It is important to note that all individuals carry 4-5 abnormal genes among the 30,000 or so genes that we have. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.

The frequency of OCA1 is approximately 1/40,000 in the world population. Most of the individuals identified with OCA1 have OCA type 1A. The frequency of OCA type 1B is unknown.

The prevalence of OCA2 in the African population is approximately 1/1,500-1/8,000. The prevalence in the African American population has been estimated to be as high as 1/10,000. The prevalence of OCA2 in other populations is approximately 1/38,000-1/40,000.

The prevalence of OCA3 is not known.

The prevalence of OCA4 is approximately 1/100,000 in most world populations. OCA4 is more common in Japan.

Symptoms of the following disorders can be similar to those of oculocutaneous albinism. Comparisons may be useful for a differential diagnosis:

Hermansky-Pudlak syndrome is a rare, hereditary disorder that consists of three characteristics: reduced skin, hair and eye pigmentation (oculocutaneous albinism, with associated vision problems), blood platelet dysfunction leading to prolonged bleeding, , and abnormal storage of a fatty-like substance (ceroid lipofuscin) in various tissues of the body. (For more information on this disorder, choose "Hermansky" as your search term in the Rare Disease Database.) Several different genes have been associated with Hermansky-Pudlak syndrome

Ocular albinism is an X-linked recessive disorder that affects the pigment cells of the eyes. Affected individuals (mostly males) have vision problems and hair and skin color may be fairer than that of other family members. (For more information on this disorder, choose "albinism, ocular" as your search term in the Rare Disease Database.)

Congenital motor nystagmus is a genetic condition characterized by an involuntary movement of eyes back and forth (nystagmus). Affected individuals will often turn or bob their head to try to improve vision clarity.

Diagnosis
The diagnosis of OCA1 is based on lack of pigment in the skin and the characteristic eye abnormalities. Molecular genetic testing for the TYR gene is available but is not usually necessary for diagnosis. TYR gene testing is used for carrier testing and prenatal diagnosis.

The diagnosis of OCA2 is based on physical findings. Testing for the gene deletion associated with OCA2 in individuals of African ancestry is available to confirm the diagnosis. Carrier testing and prenatal diagnosis are available if the deletion is identified. Molecular genetic testing for all mutations in the OCA2 gene is available on a research basis only.

The diagnosis of OCA3 is based on physical findings in individuals of African ancestry.

OCA4 can not be differentiated from OCA2 based on physical findings. Molecular genetic testing for the SLC45A2 gene is available on a research basis only.

Treatment
Individuals diagnosed with OCA should be evaluated by an ophthalmologist at the time of diagnosis to determine the extent of the disease and have ongoing ophthalmologic examinations annually. Glasses or contact lenses can improve vision. Dark glasses or a hat with a wide brim can help to reduce sun sensitivity. Affected individuals should also be evaluated to determine the amount of pigment in the skin. Skin should be protected from sun exposure with the use of clothing and sun block to reduce the risk of sunburn, skin damage and skin cancer. Specific recommendations for skin care depend on the pigment status.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

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