(See also Overview of Pigmentation Disorders Overview of Pigmentation Disorders Melanin is the brownish pigment responsible for the color of skin, hair, and the iris of the eyes. It is produced by melanocytes. Most people have similar numbers of melanocytes, and the wide... read more .)
Pathophysiology of Albinism
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. OCA occurs in people of all races throughout the world. Cutaneous and ocular pathologies (ocular involvement) are both present. Findings in ocular involvement include abnormal optic tract development manifested by foveal hypoplasia with decreased photoreceptors and misrouting of optic chiasmal fibers.
Most cases of OCA are autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more ; autosomal dominant Autosomal Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more inheritance is rare. There are 8 genetic forms of OCA, of which the first 4 are well characterized:
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 but may involve regulation of organelle pH and accumulation of vacuolar glutathione. Tyrosinase activity is present. Type II is the most common form of OCA in Africa.
Type III occurs only in people with otherwise dark skin (Fitzpatrick skin types III to V—see table Fitzpatrick Skin Type Classification Fitzpatrick Skin Type Classification ). It is caused by mutations in the tyrosinase-related protein 1 gene whose product is important in the synthesis of eumelanin, the most common of the 3 types of melanin that give skin, hair, and eyes their color.
Type IV is an extremely rare form in which the defect is in a gene (SLC45A2) that codes a membrane transporter protein involved in tyrosinase processing and trafficking of proteins to melanosomes. Type IV is the most common form of OCA in Japan.
Type V has been linked to chromosome 4q24, a region that may code for lysosomal proteins.
Type VI has been linked to mutations in gene SLC45A5, which encodes a membrane transporter protein.
Type VII is due to mutations in gene C10orf11, which encodes a leucine-rich protein that may play a role in melanocyte differentiation.
Type VIII has been linked to a mutation in the dopachrome tautomerase (DCT) gene on chromosome 13q32, which encodes an enzyme that plays a role in modification of skin pigment color.
Nettleship-Falls (OA1) and Forsius-Eriksson (OA2) are extremely rare compared to OCA. They are inherited in an X-linked dominant X-Linked Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more fashion. Usually findings are confined to the eyes, but skin may be hypopigmented. Patients with OA1 may have late-onset sensorineural deafness.
In another group of inherited diseases, a clinical phenotype of OCA occurs in conjunction with bleeding disorders. In Hermansky-Pudlak syndrome, OCA-like findings occur with platelet abnormalities and a ceroid-lipofuscin lysosomal storage disease (which can lead to pulmonary fibrosis Idiopathic Pulmonary Fibrosis Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, causes progressive pulmonary fibrosis. Symptoms and signs develop over months to years and include... read more and granulomatous colitis). This syndrome is rare except in people with family origin in Puerto Rico, where its incidence is approximately 1 in 1800 (1 General reference Oculocutaneous albinism is an inherited defect in melanin formation that causes diffuse hypopigmentation of the skin, hair, and eyes. Ocular albinism affects the eyes and usually not the skin... read more ). In Chédiak-Higashi syndrome Chédiak-Higashi Syndrome Chédiak-Higashi syndrome is a rare, autosomal recessive immunodeficiency disorder characterized by impaired lysis of phagocytized bacteria, resulting in recurrent bacterial respiratory and other... read more , OCA-like cutaneous and ocular findings occur, hair is silvery gray, and a decrease in platelet-dense granules results in a bleeding diathesis. Patients with Chédiak-Higashi syndrome have severe immunodeficiency due to abnormal lymphocyte lytic granules and progressive neurologic degeneration.
1. Witkop CJ, Almadovar C, Piñeiro B, et al : Hermansky-Pudlak syndrome (HPS). An epidemiologic study. Ophthalmic Paediatr Genet 11(3):245-250. doi: 10.3109/13816819009020986
Symptoms and Signs of Albinism
The different genetic forms of oculocutaneous albinism have a variety of phenotypes.
OCA type I (OCA1A) is classic tyrosinase-negative albinism; skin and hair are milky white, and eyes are blue-gray (decrease in visual acuity is the most severe in this form of oculocutaneous albinism). Pigmentary dilution in OCA1B ranges from obvious to subtle.
OCA 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 OCA type III, skin is brown, hair is rufous (reddish), and eye color can be blue or brown.
In OCA type IV, the phenotype is similar to that for type II.
In OCA type V, skin is white, and hair is golden-colored.
In OCA type VI, skin can be white, and hair can be light at birth and may darken with age.
In OCA type VII, skin pigment is decreased, and hair can range from white to brown.
In OCA type VIII, skin and hair are mildly hypopigmented.
Patients with ocular involvement may have decreased retinal pigmentation, leading to sensitivity to light and light avoidance. In addition, nystagmus Nystagmus Nystagmus is a rhythmic movement of the eyes that can have various causes. Vestibular disorders can result in nystagmus because the vestibular system and the oculomotor nuclei are interconnected... read more , strabismus Strabismus Strabismus is misalignment of the eyes, which causes deviation from the parallelism of normal gaze. Diagnosis is clinical, including observation of the corneal light reflex and use of a cover... read more , reduced visual acuity, and loss of binocular stereopsis likely result from defective routing of the optic fibers.
Diagnosis of Albinism
Diagnosis of all types of OCA and OA is based on examination of the skin and eyes. Early ocular examination may detect iris translucency, reduced retinal pigmentation, foveal hypoplasia, reduced visual acuity, strabismus, and nystagmus.
Treatment of Albinism
Strict sun protection
Sometimes surgical intervention for strabismus
There is no cure for albinism.
Patients are at high risk of sunburn Sunburn Sunburn is characterized by erythema and sometimes pain and blisters caused by overexposure to solar ultraviolet radiation. Treatment is similar to that for thermal burns, including cool compresses... read more and skin cancers (especially squamous cell carcinoma Squamous Cell Carcinoma Squamous cell carcinoma is a malignant tumor of epidermal keratinocytes that invades the dermis; this cancer usually occurs in sun-exposed areas. Local destruction may be extensive, and metastases... read more ) and should avoid direct sunlight, use sunglasses with ultraviolet (UV) filtration, wear sun-protective clothing with a UV protection factor of 50 or higher, and use sunscreen with a broad-spectrum sun protection factor (SPF) as high as possible (eg, 50 or higher) that protects against UVA and UVB wavelengths (see sun exposure prevention Prevention The skin may respond to sunlight with chronic (eg, dermatoheliosis [photoaging], actinic keratosis) or acute (eg, photosensitivity, sunburn) changes. The sun emits a wide range of electromagnetic... read more ).
Patients with OCA should have regular skin examinations. Of note, melanoma that develops in patients with OCA is frequently amelanotic; common sites include the back and legs.
Oculocutaneous albinism is a group of rare, usually autosomal recessive disorders, resulting in hypopigmentation of the skin, hair, and eyes.
Ocular involvement causes photosensitivity and often nystagmus, strabismus, reduced visual acuity, and loss of binocular stereopsis.
Examine the eyes and skin to make the diagnosis.
Instruct patients on how to strictly protect the skin and eyes from sun exposure.