Types of Albinism

Photo courtesy of The Guardian Opens in new window

Albinism is an inherited defect which results in little or no pigment in hair, eyes, or skin and causes significant visual problems. There are two major forms of albinism Opens in new window, they include:

1. oculocutaneous albinism, in which pigment is reduced in the hair, skin and eyes; and
2. ocular albinism, in which pigment is reduced only in the eyes.

Overall, some type of albinism occurs in approximately 1 in 17,000 live births. Prevalence in African Americans in the United States is about 1/10,000; in Hopi Amerindians 1/227, and 1/240 among Zuni Amerindians.

Oculocutaneous Albinism

Researchers have described 10 types of oculocutaneous albinism. The most common types are termed either OCA1 and OCA2. These were formerly referred to as ty-negative and ty-positive respectively, based on whether or not the enzyme tyrosinase is present. This is an enzyme that converts tyrosine, an amino acid, into melanin in the production of pigment.

Differentiation between OCA1 and OCA2 on the basis of physical examination is not always possible as there is a considerable overlap between the phenotypes, or characteristics of the two. The most helpful feature is that most individuals with OCA1 (ty-neg) have white hair, milky white skin, and blue eyes at birth.

The determination is made by plucking a few hairs from the scalp of a person with albinism, and incubating the roots, or bulbs, in a chemical solution of tyrosine. Hair bulbs that don’t turn dark in this test are termed ty-neg, — that is, they don’t produce melanin from tyrosine. If the hair bulbs turn dark, they are termed ty-post—melanin is present. A tyrosine assay measures the rate at which tyrosine in hair bulbs is converted to dopa, which is then made into pigment.

The hair bulb incubation and tyrosinase assays that have been used to differentiate between OCA1 and OCA2 are not precise, and overlap exists in their results. The genes that cause OCA1 and OCA2 have been identified, and molecular testing of the involved genes provides the most accurate means of diagnosis

1. OCA1 (formerly Tyrosine-negative oculocutaneous albinism)

Without tyrosinase activity, the skin and hair stay white throughout life. There is a greater susceptibility to developing skin cancer than in ty-pos albinism. The genetic abnormality in OCA1 is in the tyrosinase gene Opens in new window found on the long arm of chromosome 11. Many different mutations have been found.

Classical OCA1 individuals have mutations which result in complete absence of enzyme activity. Some individuals have mutations which reduce but do not eliminate enzyme activity.

While generally they have white skin and hair at birth, some hair pigment may develop in the first years of life and their appearance may be that of so-called yellow albinism with blond hair. yellow albinism has been particularly described in the Amish.

Carriers Opens in new window can be identified through hair bulb analysis, measuring the rate at which they produce pigment, and prenatal diagnosis is possible through testing fetal hair bulbs obtained by festoscopy. Visual problems are severe. OCA1 albinism occurs in about one in 28,000 blacks and one in 39,000 whites in the United States.

2. OCA2 (formerly Tyrosine-positive oculocutaneous albinism)

At early ages, this form closely resembles ty-neg albinism. However, there is partial activity of tyrosinase Opens in new window, leading to the gradual accumulation of pigment with age. The hair becomes yellow or reddish and the skin may become freckled or have pigmented nevi.

Ocular problems are less severe than in ty-neg, and tend to improve with age. This form is estimate to occur in one in 15,000 blacks and one in 37,000 whites in the United States. It is particularly common in some Indian tribes.

Individuals with OCA2 have mutations in a gene found on the long arm of chromosome 15, known as the P gene.

Like tyrosinase, many different mutations Opens in new window have been found. The gene appears to encode a transporter protein integral to the membrane of the melanosome, the intracellular organelle that contains the pigment cell’s melanin.

Chediak-Higashi syndrome Opens in new window is a rare form of OCA2 (formerly ty-pos albinism). While oculocutaneous symptoms are moderate, it is usually fatal in childhood due to leukocyte abnormalities that lead to repeated infections and a condition that mimics leukemia. The gene involved in Chediak-Higashi syndrome is the lysosomal trafficking regulator gene found on chromosome 19.

Hermansky-Pudlak-type albinism Opens in new window exhibits a progressive and potentially life-threatening bleeding tendency. Most affected individuals are of Puerto Rican descent, but it has been found rarely in other populations.

The frequency in Puerto Rico is about 1/2000, making it the most frequent single gene disorder in Puerto Rico. Lung disease and intestinal problems (colitis) are also features of this disorder. The gene involved was discovered in 1996; it is found on chromosome 10 and appears to encode an important protein component of multiple organelles found in the cell.

Ocular Albinism

In these forms of albinism pigment is reduced only in the eyes. There are several recognized types. The most prevalent forms are X-linked Opens in new window and therefore affect primarily males.

The gene for X-linked OA Opens in new window, named OA1, has been identified on the short arm of the X chromosome Opens in new window. Female carriers can generally be identified through subtle abnormalities in the eye that are detectable through ophthalmologic examination.

An autosomal recessive form previously thought to be a type of ocular albinism affects males and females equally. In this form, mutations have been found in either the tyrosinase or P genes. Thus, this is actually a form of OCA with minimal cutaneous features and primarily ocular involvement.