Albinism

Signs and Symptoms
Albinism affects approximately 1 in 20,000 individuals, producing pigmentary deficiency, abnormal crossings of the temporal fibers in the optic chiasm, nystagmus, photophobia, variable visual acuity and, frequently, strabismus. The main subdivisions of albinism include oculocutaneous, ocular, and albinoidism (absence of pigment in localized areas; the pigment in the skin, hair and eyes is less than normal but does not affect the individual as severely as the oculocutaneous or ocular types). The literature reports as many as 20 variants of oculocutaneous albinism alone.

Oculocutaneous as well as ocular albinos exhibit similar ocular and visual dysfunction. The oculocutaneous albino patient manifests reduced acuity, photophobia, strabismus, significant refractive error with astigmatism, transillumination of the iris and globe, nystagmus, blonde fundus with visible choroidal vasculature, and macular hypoplasia. A super-normal EOG and ERG is also present.

Transillumination of the iris and globe results from insufficient uveal pigmentation and poor development of the retinal pigment epithelium. This leads to a funduscopic picture of a blond fundus with extensive areas of hypopigmentation and clearly visible underlying choroidal vasculature. The pigment of the RPE acts as a sink for incoming light. When the RPE is underdeveloped, light scatters within the eye, producing the subjective complaint of photophobia.

The level of visual acuity varies among albino patients according to the amount of ocular pigmentation present and the concomitant level of macular development. Ocular albinos have variable amounts of uveal pigmentation and the potential to have the best acuity (20/25 to 20/300) among albinos. Oculocutaneous albinos exhibits less pigmentation than their ocular albino counterparts and tend to have lower acuity levels (20/80 to 20/400).

Systemically, albino patients may exhibit difficulties with healing and infection, as well as bleeding (Chédiak-Higashi syndrome and Hermansky-Pudlak respectively). Clinicians should ask questions in the history regarding bruising, nosebleeding and healing.

Pathophysiology
Albinism is a disorder of amino acid metabolism that results in a congenital hypopigmentation of ocular and systemic tissues. Cellular pigmentation is dependant upon a cell’s ability to manufacture and sequester the pigment melanin. This is accomplished within organelles called melanosomes which reside inside cells called melanocytes. The melanocytes that originate in the neural crest provide pigment for the skin (including eyelids), hair, uvea, conjunctiva, stroma of the iris, ciliary body and choroid. The melanocytes that supply pigment for the retinal pigment epithelium (RPE) are derived from neuroectoderm. Inside the melanosome, melanin is synthesized from the amino acid tyrosine through the actions of the enzyme tyrosinase. On the basis of the results of either the tyrosine hair bulb test or electron microscopy of the hair bulb or skin, oculocutaneous albinos are classified as tyrosinase-positive or tyrosinase-negative.

Tyrosinase-positive and -negative oculocutaneous albinos possess an autosomal recessive inheritance pattern. Oculocutaneous albinism results from incomplete melanization of the cellular melanosomes. In tyrosinase-negative oculocutaneous albinism, the congenital inactivity of the enzyme tyrosinase prevents the cell’s use of tyrosine in the formation of the pigment melanin. In tyrosinase-positive oculocutaneous albinism, tyrosinase activity is normal, but there is an inability of the cells to sequester the synthesized melanin into the melanosomes.

An autosomal recessive subtype of tyrosinase positive oculocutaneous albinism commonly seen in Puerto Rico is the Hermansky-Pudlak syndrome. Here, patients exhibit hemorrhagic diathesis (a tendency toward easy bruising and bleeding) due to a platelet dysfunction along with normal tyrosinase activity.

Another autosomal recessive subtype of oculocutaneous albinism is the Chédiak-Higashi syndrome. Here, patients may have a silvery sheen to their skin, and blue to brown irides. Normal tyrosinase activity within hair bulbs shows increased susceptibility to infection, hepatosplenomegaly, lymphadenopathy and a predisposition to development of a lymphoma-like condition.

Ocular albinism, in contrast to oculocutaneous albinism, exhibits pigmentary dilution due to abnormalities in melanosome synthesis rather than inadequate melanization. Ocular albinism is transmitted through either an X-linked or autosomal recessive mode. The hair and skin of the ocular albino tends to show a much greater pigmentation than that of the oculocutaneous albino, often falling into a normal pigmentation range. The uveal pigmentation of the ocular albino is variable and may range from very hypopigmented to a nearly normal pigmentation level.

Both ocular and oculocutaneous albinism exhibit a hypoplastic macula. Orderly retinal morphogenesis depends on the organizing influence of the adjacent retinal pigment epithelium. The insufficient uveal pigmentation and poor development of the RPE in the albinotic patient provides a developmentally unstable substrate for normal retinal organization. Hence, the albinotic macula is always hypoplastic and the albinotic patient has secondarily reduced acuity. This maldevelopment of the macula explains the pendular nystagmus of the albino patient, as the albino eye constantly searches for a clear image.