Ocular Manifestations of Albinism

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Albinism refers to a group of hereditary disorders that involve an abnormality of melanin synthesis or distribution.

The term albinism comes from the Latin word albus, which means white, and, in 1908, Garrod first scientifically described it. [1] Clinically, albinism presents as a pigmentation abnormality of the skin, the hair, and/or the eyes. Albinism can be divided into 2 broad categories, as follows: oculocutaneous albinism and ocular albinism. Oculocutaneous albinism involves both the skin and the eyes, whereas ocular albinism mainly affects the eyes with minimal to no skin involvement.

The primary morbidity of both oculocutaneous albinism and ocular albinism is eye related. Signs and symptoms include photophobia, refractive errors, monocular vision, strabismus, pendular nystagmus, iris transillumination defects, foveal hypoplasia, and abnormal decussation of the optic nerve fibers. These ocular manifestations are almost always present in both forms of albinism; however, the degree of their presentation can vary depending on the type of albinism and the racial background of the patient.

The inheritance pattern of albinism is also quite variable. Oculocutaneous albinism is mostly an autosomal recessive disorder, whereas ocular albinism is transmitted as a sex-linked or autosomal recessive disease.

Oculocutaneous albinism is divided into approximately 10 different types. Two of the more common forms are type I (tyrosinase negative) [2] and type II (tyrosinase positive) oculocutaneous albinism. Patients with type I disease have no skin or ocular pigmentation, whereas those with type II disease can develop some pigmentation as they grow older.

Another important form of oculocutaneous albinism is type IB, which was previously called yellow mutant oculocutaneous albinism. Patients with type IB are similar to those with type I but can exhibit some pigmentation of their skin, hair, and ocular structures.

Two additional rare types of oculocutaneous albinism with important systemic findings and an increased risk of mortality are Hermansky-Pudlak syndrome and Chediak-Higashi syndrome.

Ocular albinism type I is an X-linked disorder associated with the OA1 gene. Type I is the most common form of ocular albinism. Female carriers can show minor signs, whereas males with ocular albinism can show a constellation of any of the above-mentioned findings.

The visual acuity in patients with albinism is variable and ranges from 20/40 to 20/400. [3, 4]

Melanin is the pigment responsible for skin, hair, and eye coloration. Albinism is caused by a disorder of melanin metabolism, and the defect can lie with either melanin synthesis or distribution. Melanin is synthesized in melanocytes from the amino acid tyrosine. This process takes place in special organelles called melanosomes. The pathophysiology of oculocutaneous albinism involves a reduction in the amount of melanin present in each of the melanosomes. The pathophysiology of ocular albinism is a reduction in the number of melanosomes, although each melanosome may be fully pigmented.

The most important enzyme in the synthesis of melanin is tyrosinase, which converts tyrosine to dopa. The gene for the enzyme tyrosinase has been localized to chromosome 11. A number of mutations have been found at this locus, which can result in an absent or defective tyrosinase enzyme. This results in type I oculocutaneous albinism, which is characterized by complete absence of skin and eye pigmentation, despite a normal number of melanosomes.

In contrast, the type II (tyrosine positive) oculocutaneous albinism defect is within the P polypeptide, which is a melanosomal tyrosine transporter. The P gene has been mapped to chromosome 15 and is more commonly linked with albinism in patients of African descent. These patients do have some pigment, but they have lighter pigmentation than expected due to their relatives and ethnicity.

Ocular albinism type I is an X-linked disorder related to defects in the OA1 gene. This gene produces pigment cell-specific, intracellular G-protein coupled receptor 143 (GPR143), [5] which appears to result in faulty transport of melanosomes and lysosomes as well as macromelanosomes. Patients with this disorder are found to have giant melanosomes in their skin melanocytes and retinal pigment epithelium.

The exact mechanism by which the absence of pigmentation leads to foveal hypoplasia and abnormal decussation of optic nerve fibers is not completely understood. It has been postulated that retinal pigment epithelial pigmentation around the macula is necessary for the normal development of the fovea. It also has been suggested that the absence of dopa, which is an antimitotic agent, can influence normal retinal development. This foveal hypoplasia is responsible for some degree of decreased visual acuity in almost all types of albinism. The abnormal decussation of optic nerve fibers is responsible for strabismus and monocular vision. Photophobia results from iris transillumination defects.

United States

The frequency of type I (tyrosinase negative) oculocutaneous albinism is approximately 1 in 17,000 to 1 in 20,000.

The frequency of type IB albinism appears to be higher among Amish people.

The frequency of type II (tyrosinase positive) oculocutaneous albinism is higher in the African American population, where it can be 1 in 10,000, as compared to 1 in 36,000 in Caucasian Americans.

The prevalence of X-linked ocular albinism is estimated to be 1 in 50,000.


The frequency of type I oculocutaneous albinism worldwide is about the same as in the United States.

The frequency of type II oculocutaneous albinism is higher in African countries, where it can range from 1 in 2000 to 1 in 5000.

Similarly, the frequency of Hermansky-Pudlak syndrome is much higher in Puerto Rico, where it is approximately 1 in 2700.

The main cause for morbidity in patients with albinism is decreased visual acuity.

In tropical regions, there can be higher mortality among these patients secondary to an increased incidence of skin cancer due to sun exposure.

Mortality also is increased in patients with Hermansky-Pudlak syndrome and Chediak-Higashi syndrome. Patients with Hermansky-Pudlak syndrome have a bleeding diathesis secondary to platelet dysfunction and also experience restrictive lung disease, inflammatory bowel disease, cardiomyopathy, and renal disease. Patients with Chediak-Higashi syndrome are susceptible to infection and also can develop lymphofollicular malignancy.

Albinism affects all racial groups. However, type II oculocutaneous albinism occurs more frequently in African American and African populations. Similarly, there is a much higher incidence of Hermansky-Pudlak syndrome among people of Puerto Rican origin.

Oculocutaneous albinism affects both sexes equally. Ocular albinism is a disease primarily of males because of its sex-linked transmission.

Most people with albinism are diagnosed during infancy or early childhood.

Visual prognosis in patients with albinism is quite variable. Usually, no improvement in visual acuity occurs in patients with type I oculocutaneous albinism. Visual acuity may improve with increased pigmentation in other forms of albinism as the patient grows older.

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Mohammed O Peracha, MD Associate Physician, Midwest Eye Center

Mohammed O Peracha, MD is a member of the following medical societies: American Academy of Ophthalmology

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Frances M Cosgrove, MD Resident Physician, Department of Ophthalmology, Indiana University School of Medicine

Frances M Cosgrove, MD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology

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Enrique Garcia-Valenzuela, MD, PhD Clinical Assistant Professor, Department of Ophthalmology, University of Illinois Eye and Ear Infirmary; Consulting Staff, Vitreo-Retinal Surgery, Midwest Retina Consultants, SC, Parkside Center

Enrique Garcia-Valenzuela, MD, PhD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Society of Retina Specialists, Retina Society, Society for Neuroscience

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Dean Eliott, MD Associate Director, Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School

Dean Eliott, MD is a member of the following medical societies: American Academy of Ophthalmology, American Medical Association

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Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

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J James Rowsey, MD Former Director of Corneal Services, St Luke’s Cataract and Laser Institute

J James Rowsey, MD is a member of the following medical societies: American Academy of Ophthalmology, American Association for the Advancement of Science, American Medical Association, Association for Research in Vision and Ophthalmology, Florida Medical Association, Sigma Xi, Southern Medical Association, Pan-American Association of Ophthalmology

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Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

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Kilbourn Gordon, III, MD, FACEP Urgent Care Physician

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Ocular Manifestations of Albinism

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