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Albinism (officially called oculocutaneous albinism) is an inherited defect in melanin formation that causes diffuse hypopigmentation of the skin, hair, and eyes; deficiency of melanin (and hence pigmentary dilution) may be total or partial, but all areas of the skin are involved. Ocular involvement causes strabismus, nystagmus, and decreased vision. Diagnosis is usually obvious from the skin, but ocular evaluation is necessary. No treatment for the skin involvement is available other than protection from sunlight.

Pathophysiology

Oculocutaneous albinism (OCA) is a group of rare inherited disorders in which a normal number of melanocytes are present but melanin production is absent or greatly decreased. Cutaneous and ocular pathologies (ocular albinism) are both present. Ocular albinism involves abnormal optic tract CNS development manifested by foveal hypoplasia with decreased photoreceptors and misrouting of optic chiasmal fibers. Ocular albinism may occur without cutaneous abnormalities.

Albinism (Cutaneous)

Albinism (Ocular)

Most cases are autosomal recessive; autosomal dominant inheritance is rare. There are 4 main genetic forms:

• Type I is caused by absent (OCA1A; 40% of all OCA) or reduced (OCA1B) tyrosinase activity; tyrosinase catalyzes several steps in melanin synthesis.
• Type II (50% of all OCA) is caused by mutations in the P (pink-eyed) gene. The function of the P protein is not yet known. Tyrosinase activity is present.
• Type III occurs only in people with dark skin (skin types III to V). It is caused by mutations in a tyrosinase-related protein 1 gene whose product is important in eumelanin synthesis.
• Type IV is an extremely rare form in which the genetic defect is in a gene that codes a membrane transporter protein. Type IV is the most common form of OCA in Japan.

In a group of inherited diseases, a clinical phenotype of OCA occurs in conjunction with bleeding disorders. In the Hermansky-Pudlak syndrome, OCA-like findings occur with platelet abnormalities and a ceroid-lipofuscin lysosomal storage disease. This syndrome is rare except in people with family origin in Puerto Rico, where its incidence is 1 in 1800. In the Chédiak-Higashi syndrome, OCA-like findings occur (hair is silvery gray), and a decrease in platelet-dense granules results in a bleeding diathesis. Patients have severe immunodeficiency due to abnormal lymphocyte lytic granules. Progressive neurologic degeneration occurs.

Symptoms and Signs

The different genetic forms have a variety of phenotypes.

Type I (OCA1A) is classic tyrosinase-negative albinism; skin and hair are milky white, and eyes are blue-gray. Pigmentary dilution in OCA1B ranges from obvious to subtle.

Type II has phenotypes with pigmentary dilution that ranges from minimal to moderate. Pigmented nevi and lentigines may develop if skin is exposed to the sun; some lentigines become large and dark. Eye color varies greatly.

In type III, skin is brown, hair is rufous (reddish), and eye color can be blue or brown.

In type IV, the phenotype is similar to that for type II.

Those with ocular involvement may have decreased retinal pigmentation, leading to photophobia. In addition, nystagmus, strabismus, reduced visual acuity, and loss of binocular vision likely result from defective routing of the optic fibers.

Diagnosis

• Clinical evaluation

Diagnosis of all types of OCA is based on examination of the skin. Early ocular examination may detect iris translucency, reduced retinal pigmentation, foveal hypoplasia, reduced visual acuity, and ocular movement disorders (strabismus and nystagmus).

Treatment

• Sun protection
• Sometimes surgical intervention for ocular movement disorders

There is no treatment for albinism. Patients are at high risk of sunburn and skin cancers (especially squamous cell carcinoma) and should avoid direct sunlight, use sunglasses with UV filtration, wear protective clothing, and use sunscreen with an SPF of ≥ 30 that protects against UVA and UVB wavelengths (see Reactions to Sunlight: Prevention). Some surgical interventions may lessen ocular movement disorders.

Last full review/revision October 2008 by Daniel E. McGinley-Smith, MD

Content last modified October 2008