Albinism

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

Albinism
Classification & external resources

Albinistic boy
ICD- 10	E 70.3
ICD- 9	270.2
OMIM	203100 103470, 203200, 203280, 203290, 203300, 203310, 256710, 278400, 214450, 214500, 220900, 300500, 300600, 300650, 300700, 600501, 604228, 606574, 606952, 607624, 609227
DiseasesDB	318
MedlinePlus	001479
eMedicine	derm/12

Albinism (from Latin albus; extended etymology), more technically hypomelanism or hypomelanosis, is a form of hypopigmentary congenital disorder, characterized by a lack of melanin pigment in the eyes, skin and hair (or more rarely the eyes alone). Albinism results from inheritance of recessive genes. The condition is known to affect mammals, fish, birds, reptiles, and amphibians. While the most common term for an organism affected by albinism is "albino" (noun and adjective), the word is sometimes used in a derogatory way towards people; more neutral terms are "albinistic" (adjective) and "person with albinism" (noun). Additional clinical adjectives sometimes used to refer to animals are "albinoid" and "albinic".

Causes

Albinism is a genetic disorder; it is not an infectious disease and cannot be transmitted through contact, blood transfusions, etc. The principal gene which results in albinism prevents the body from making the usual amounts of the pigment melanin. Most forms of albinism are the result of the biological inheritance of genetically recessive alleles ( genes) passed from both parents of an individual, though some rare forms are inherited from only one parent. There are other genetic mutations which are proven to be associated with albinism. All alterations, however, lead to changes in melanin production in the body.

Albinism used to be categorized as tyrosinase-positive or -negative. In cases of tyrosinase-positive albinism, the enzyme tyrosinase is present. The melanocytes (pigment cells) are unable to produce melanin for any one of a variety of reasons that do not directly involve the tyrosinase enzyme. In tyrosinase negative cases, either the tyrosinase enzyme is not produced or a nonfunctional version is produced. This classification has been rendered obsolete by recent research.

The chance of offspring with albinism resulting from the pairing of an organism with albinism and one without albinism is low, as discussed in more detail below. However, because organisms can be carriers of genes for albinism without exhibiting any traits, albinistic offspring can be produced by two non-albinistic parents. Albinism usually occurs with equal frequency in both genders. The only exception from this is ocular albinism, because it is passed on to offspring through X-linked inheritance. Thus, males more frequently have ocular albinism.

Because organisms with albinism have skin that lacks (sufficiently or entirely) the dark pigment melanin, which helps protect the skin from ultraviolet radiation coming from the sun, they can sunburn easily from overexposure. (See human skin colour for more information). Lack of melanin in the eye also results in problems with vision, related and unrelated to photosensitivity, which are discussed further below.

Most organisms with albinism appear white or very pale; the multiple types of melanin pigment are responsible for brown, black, gray, and some yellow colorations. In some animals, especially birds and reptiles, ruddy and yellow hues or other colors may be present on the entire body or in patches (as is common among pigeons), due to the presence of other pigments unaffected by albinism such as porphyrins, pteridines and psittacins, and carotenoids derived from the diet. Some animals are white or pale due to chromatophore (pigment cell) defects, do not lack melanin production, and have normal eyes; they are referred to as leucistic. The direct opposite of albinism, an unusually high level of melanin pigmentation (and sometimes absence of other types of pigment in species that have more than one), is known as melanism, and results in an appearance darker than non-melanistic specimens from the same genepool. Albinism-like conditions may affect other pigments or pigment-production mechanisms in some animals (e.g. "whiteface", a lack of psittacins that can affect some parrot species.). Another is common in reptiles and amphibians: axanthism, in which xanthophore metabolism, instead of synthesis of melanin, is affected, resuling in reduction or absence of red and yellow pteridine pigments. Of all these conditions, only albinism and melanism affect humans.

The eyes of an animal with albinism occasionally appear red due to the underlying retinal blood vessels showing through where there is not enough pigment to cover them. In humans this is rarely the case, as a human eye is quite large and thus produces enough pigment to lend opacity to the eye. However, there are cases in which the eyes of an albinistic person appear red or purple, depending on the amount of pigment present. The albinistic are generally (but see related disorders below) as healthy as the rest of their species, with growth and development occurring as normal, and albinism by itself does not cause mortality (though the lack of pigment is an elevated risk for skin cancer and other problems.) Many animals with albinism lack their protective camouflage and are unable to conceal themselves from their predators or prey; the survival rate of animals with albinism in the wild is usually quite low. However the novelty of albino animals has occasionally led to their protection by groups such as the Albino Squirrel Preservation Society.

Intentionally-bred albinistic strains of some animal species are commonly used as model organisms in biomedical study and experimentation. Examples include the BALB/c mouse and Wistar and Sprague Dawley rat strains, while albino rabbits were historically used for Draize toxicity testing. Albino axolotls, zebrafish, medaka and frogs are other common laboratory animals.

Types of human albinism

About 1 in 17,000 human beings has some type of albinism, although up to 1 in 70 is a carrier of albinism genes.

There are two main categories of albinism in humans:

• In oculocutaneous albinism (despite its Latin-derived name meaning "eye-and-skin" albinism), pigment is lacking in the eyes, skin and hair. (The equivalent mutation in non-humans also results in lack of melanin in the fur, scales or feathers.)
• In ocular albinism, only the eyes lack pigment. People with oculocutaneous albinism can have anywhere from no pigment at all to almost-normal levels. People who have ocular albinism have generally normal skin and hair colour, and many even have a normal eye appearance.

While there is only one major type of ocular albinism, there are several varieties of oculocutaneous albinism (and disorders which produce the same or similar results), some of which have subtypes. Some are easily distinguished by appearance, but in most cases, genetic testing is the only way to be certain.

Oculocutaneous albinism family

• Oculocutaneous albinism type 1 (OCA1) ( Mendelian Inheritance in Man (OMIM) 203100) is the type with (usually) the least amount of pigment. People with this type generally have very pale skin, "white" (actually translucent) hair and light blue eyes, however there are cases in which the irises can appear pink or violet, depending on the amount of blue (non-melanin) pigment present in the irises and the level and direction of light available to the observer. OCA1 is caused by an alteration of the tyrosinase gene, and can occur in two variations. The first is OCA1a, and means that the organism cannot develop pigment at all. Vision usually ranges from 20/200 to 20/400. The second is OCA1b, which has several subtypes itself. Some individuals with OCA1b can tan and develop pigment. One subtype of OCA1b is called OCA1b TS (temperature sensitive), where the tyrosinase can only function below a certain temperature, which causes the body hair in cooler body regions to develop pigment (i.e. get darker). (An equivalent mutation produces the coat pattern in Siamese cats.) Another variant of OCA1b, called Albinism, yellow mutant type (OMIM: 606952) is more common among the Amish than in other populations, and results in blonde hair and the eventual development of skin pigmentation during infancy, though at birth is difficult to distinguish from other types. About 1 in 40,000 people have some form of OCA1.

• Oculocutaneous albinism type 2 (OCA2) (OMIM: 203200), the most common type of albinism, is caused by mutation of the P gene. People with OCA2 generally have more pigment and better vision than those with OCA1, but cannot tan like some with OCA1b. A little pigment can develop in freckles or moles. People with OCA2 usually have fair skin but not as pale as OCA1, and pale blonde to golden or reddish-blonde hair, and most commonly blue eyes. Affected people of African descent usually have a different phenotype (appearance): yellow hair, pale skin, and blue, gray or hazel eyes. About 1 in 15,000 people have OCA2.

• Oculocutaneous albinism type 3 (OCA3, or rufous albinism) (OMIM: 203290) has only been partially researched and documented. It is caused by mutation of the tyrosinase-related protein-1 (Tyrp1) gene. Cases have been reported in Africa and New Guinea. Affected individuals typically have red hair, reddish-brown skin and blue or gray eyes. Variants may be the recently-identified minimal pigment type albinism (OMIM: 203280) and rufous oculocutaneous albinism (ROCA or xanthism) (OMIM: 278400). The incidence rate of OCA3 is unknown.

• Oculocutaneous albinism type 4 (OCA4) (OMIM: 606574) is very rare outside of Japan, where OCA4 accounts for 24% of albinism cases. OCA4 can only be distinguished from OCA2 through genetic testing, and is caused by mutation of the membrane-associated transporter protein (MATP) gene.

• Hermansky-Pudlak syndrome (HPS) (OMIM: 203300) is not a type of OCA, technically, but has similar features. HPS has a great range of degrees of pigmentation, from OCA1a-like to almost-normal coloring. Vision usually ranges from 20/60 to 20/200. Apart from the hypopigmentation and impaired vision, people with HPS lack dense bodies in their blood platelets which are responsible for releasing clotting factors. For this reason, HPS patients bruise easily and have a hard time stopping bleeding once it begins ( bleeding diathesis, similarly to hemophilia). HPS has seven known forms (HPS-1 through HPS-7), each caused by a different autosomal recessive gene mutation. HPS-1 and HPS-4 may also include pulmonary fibrosis, or scarring of lung tissue that prevents the necessary expansion and contraction during breathing. It is believed that this is due to a buildup of fatty ceroid in the lungs. Colitis, or inflammation in the large intestine, is another symptom of most types of HPS, which may cause diarrhea, nausea, and blood in the stool. HPS is rare generally, but affects 1 in 1800 Puerto Ricans, and is typically fatal by middle age.

• Chediak-Higashi syndrome (CHS) (OMIM: 214500), like HPS, is not technically a form of OCA, but produces similar results. CHS, caused by mutation of the LYST gene, is very rare, and is associated with other medical problems, such as immune system dysfunction that leads to a high infant mortality rate, HPS-like hemophilia, and neurological problems, among many others, in 85% of sufferers.

• Griscelli syndrome (GS) is similar to CHS in symptoms (and also very rare). It is divided into three types, GS1 (OMIM: 214450), GS2 (OMIM: 607624) and GS3 (OMIM: 609227). Each type is due to a different autosomal recessive gene mutation. Type 1 produces mainly neurological problems in addition to albinism, while type 2 produces mainly immunological issues as well as the hypopigmentation, and type 3 only evidences hypomelanosis without either of the other sorts of problems. People affected by GS differ in appearance from those with OCA, having silvery-grey hair. A fourth and even rarer variant, partial albinism and immunodeficiency syndrome (PAID) (OMIM: 604228), has been identified and requires further study. An additional type called Elejalde syndrome (OMIM: 256710) may exist, but some researchers believe it is actually simply GS1. GS2, because of its immune system effects, results in a very high mortality rate among children and young adults that have it.

Ocular albinism family

• Ocular albinism, type 1 (OA1) (OMIM: 300500), also known as Nettleship-Falls syndrome, is the most common variety of ocular albinism, which affects the eyes but generally not the skin or hair. OA1 is usually associated with nystagmus, and difficult to otherwise detect in females; males show more readily observable symptoms. There are several other identified types of OA, though researchers are not all agreed on the distinctions and classification. Most are caused by a mutation in a gene on the X chromosome, and are X-linked recessive traits.

• Ocular albinism, type 2 (OA2) (OMIM: 300600), also known as Forsius-Eriksson syndrome or "Åland Island eye disease", mostly only affects males though females are often carriers and can sometimes be symptomatic; it is frequently linked with protanopic dichromacy (a form of colour blindness) and with night blindness ( nyctalopia).

• Ocular albinism, type 3 (OA3) (OMIM: 203310), also known as ocular albinism, autosomal recessive (OAR) is a non-X-linked variant, which may be more common among the Amish than in other populations.

• Ocular albinism with sensorineural deafness (OASD) (OMIM: 300650), and as its name implies is associated with loss of hearing.

• Waardenburg syndrome, type 2, with ocular albinism (WS2-OA) (OMIM: 103470) is a rare non-X-linked recessive gene variant.

The skin colour of people affected by OA can be slightly lighter than those of the rest of their families. The eye colour can vary greatly, and in some cases only examination of the retina or genetic testing can reveal OA for certain. Some form of OA afflicts 1 in 50,000 people, though certain isolated populations are at greater risk.

Other types

Other rare variants of albinism are theorized (by ongoing research as of 2007) to exist, such as

• Albinism-deafness syndrome (ADFN) (OMIM: 300700, which may actually be closer related to vitiligo); it is predominantly observed among Hopi Native Americans (with an incidence estimated at 1 in 200 individuals)
• Recessive total albinism with congenital deafness (OMIM: 220900)
• Albinism black-lock cell-migration disorder syndrome (ABCD) (OMIM: 600501)

Symptoms and conditions associated with albinism

Genetic testing can confirm albinism and what variety it is, but offers no medical benefits except in the cases of non-OCA disorders (see below) that cause albinism along with other medical problems which may be treatable. The symptoms of albinism can be treated by various methods detailed below.

Eye conditions common in albinism may or may not include:

• Nystagmus, irregular rapid movement of the eyes back and forth, or in circular motion.
• Strabismus, eye misalignment ("crossed eyes" or "lazy eye").
• Refractive errors such as myopia or hyperopia and especially astigmatism are more likely
• Photophobia, hypersensitivity to bright light and glare.
• Foveal hypoplasia, underdevelopment of the fovea, the centre of the retina
• Optic nerve hypoplasia, underdevelopment of the optic nerve
• Abnormal decussation (crossing) of the optic nerve fibers in the optic chiasm
• Amblyopia, decrease in acuity of one or both eyes due to poor transmission to the brain, often due to other conditions such as strabismus

Organisms with albinism usually have impaired vision due to one or more of the listed conditions. While a person with albinism may suffer from common refractive errors like nearsightedness or farsightedness, the visual problems particularly associated with albinism arise from a poorly-developed retinal pigment epithelium (RPE) due to the lack of melanin. This degenerate RPE causes foveal hypoplasia (a failure in the development of normal foveae), which results in eccentric fixation and lower visual acuity, and often a minor level of strabismus. Nystagmus is usually seen, as is photophobia or light sensitivity (see below).

The iris is a sphincter with pigmented tissue (which makes up the colour of the eyes) that contracts to limit the amount of light that can enter through the pupil and relaxes again to allow for better vision in darkness. This mechanism can be observed in humans and mammals (like in cat's eyes) and is needed because too much light is uncomfortable or even painful and decreases vision. In people with albinism, the iris does not have enough pigment to block the light, thus the decrease of pupil diameter is only partially successful in reducing the amount of light that enters the eye.. Additionally, the improper development of the RPE, which in normal eyes absorbs most of the reflected sunlight, further increases glare due to light scattering within the eye. The resulting sensitivity (photophobia) generally leads to a dislike of and discomfort in bright light, but does not prevent people with albinism enjoying the outdoors, especially when using sunglasses and/or brimmed hats.

The lack of pigment also makes the skin unusually sensitive to sunlight and thus susceptible to sunburn, so people with albinism should either avoid prolonged exposure to bright sunlight or protect their skin.

Treatment of the symptoms

Albinism is a condition that cannot be "cured" or "treated" per se, but small things can be done to improve the quality of life for those affected. Most importantly to improve vision, protect the eyes from bright lights, and avoid skin damage from sunlight. The extent and success rate of these measures depend on the type of albinism and severity of the symptoms; in particular, people with ocular albinism are likely to have normally-pigmented skin, and thus do not need to take special precautions against skin damage.

Surgical treatment

For the most part, treatment of the eye conditions consists of visual rehabilitation. Surgery is possible on the ocular muscles to decrease nystagmus, strabismus and common refractive errors like astigmatism. Strabismus surgery may improve the appearance of the eyes. Nystagmus-damping surgery can also be performed, to reduce the "shaking" of the eyes back and forth. The effectiveness of all these procedures varies greatly and depends on individual circumstances. More importantly, since surgery will not restore a normal RPE or foveae, surgery will not provide fine binocular vision. In the case of esotropia (the "crossed eyes" form of strabismus), surgery may help vision by expanding the visual field (the area that the eyes can see while looking at one point).

Sun protection

It is vital that people with albinism use sunscreen when exposed to sunlight to prevent premature skin aging or skin cancer. This poses a problem for those who cannot afford sunscreen, especially in regions with high exposure to sunlight, as in Africa. Special sun protective clothing and swimsuits are available and are a good alternative to excessive use of sunscreen.

Use of sunglasses and hats with wide brims can make the glare outside bearable. Other things that can help people with albinism are avoiding sudden changes of the lighting situation (switching the light on in complete darkness), using dimmable switches and adding tint to car windows or blinds to normal windows. Lights should be yellowish rather than blue and not point towards the usual position of a person with albinism (like their seat at a table). When possible, people with albinism generally prefer to have the light on their backs rather than face it.

Misconceptions

While some of the very rare albinism disorders that are coupled with deafness and immunodeficiency appear to be linked with inbreeding, the vast majority of sufferers of common albinism are not the product of such unions; the more usual albinism genes are widespread enough that they can easily produce albinistic offspring from parents that are not related.

A common misconception is that albinistic individuals of a species are sterile; they are in fact fully capable of reproducing. It is also thought by many that people with albinism live short life spans. This is not true in general, but may be a distorted view of a more reasonable fact that people with albinism have a higher risk of skin cancer if they do not use proper skin protection when in the sun. (Some very rare variants of albinism are lethal in and of themselves by adulthood or sooner, but they are so little-known by the general public that they are unlikely to have contributed to this belief.)