Albinism

Several types of congenital oculocutaneous albinism (OCA) consist of partial or complete failure of melanin production in the skin, hair, and eyes despite the presence of normal number, structure, and distribution of melanocytes. They may be divided into two major classes: those with abnormal protein function involved in the formation and transfer of melanin, and those with defects in melanosomes (Table 645-1). Tyrosinase is the copper-containing enzyme that catalyzes at multiple steps in melanin biosynthesis (Chapter 79.2). Tyrosinase-positive variants are characterized by darkening of the hair bulb on incubation with tyrosine.

Table 645-1 GENES ASSOCIATED WITH HYPOPIGMENTATION

Oculocutaneous albinism type 1 (OCA1) is characterized by great reduction in or absence of tyrosinase activity. OCA1A, the most severe form, is characterized by a lack of visible pigment in hair, skin, and eyes (Fig. 645-1). This manifests as photophobia, nystagmus, defective visual acuity, white hair, and white skin. The irises are blue-gray in oblique light and prominent pink in reflected light. OCA1B, or yellow mutant albinism, manifests at birth as white hair, pink skin, and gray eyes. This type is particularly prevalent in Amish communities. Progressively the hair becomes yellow-red, the skin tans lightly on exposure to the sun, and the irises may accumulate some brown pigment, with a resultant improvement in visual acuity. Photophobia and nystagmus are present but mild. OCATS is a temperature-sensitive type of albinism. The abnormal tyrosinase has decreased activity at 35-37°C. Therefore, cooler regions of the body such as the limbs and head pigment to some degree, whereas other areas remain depigmented.

Figure 645-1 White hair and skin in oculocutaneous albinism type 1 (OCA1).

OCA2 ranges from nearly normal to closely resembling type 1 albinism. This is the most common form of albinism seen worldwide. Little or no melanin is present at birth, but pigment, particularly red-yellow pigment, may accumulate during childhood to produce straw-colored or light brown skin in white individuals. Pigmented nevi may develop. Progressive improvement in visual acuity and nystagmus occurs with aging. Black individuals may have yellow-brown skin, dark-brown freckles in sun-exposed areas, and brown coloration of the irises. Brown OCA is an allelic variant of OCA2. Prader-Willi and Angelman syndromes, which include hypopigmentation, have deletions that include the gene involved in OCA2.

OCA3 (rufous albinism) is seen predominantly in patients of African descent. It is characterized by red hair, reddish brown skin, pigmented nevi, freckles, reddish brown to brown eyes, nystagmus, photophobia, and decreased visual acuity.

OCA4 is a rare OCA with clinical findings similar to those in OCA2.

The Cross-McKusick-Breen syndrome consists of tyrosinase-positive albinism with ocular abnormalities, retardation, spasticity, and athetosis. The genetic defect is unidentified.

Because of the absence of normal protection by adequate amounts of epidermal melanin, persons with albinism are predisposed to development of actinic keratoses and cutaneous carcinoma secondary to skin damage by ultraviolet light. Protective clothing and a broad-spectrum sunscreen preparation (Chapter 648) should be worn during exposure to sunlight.