Albinism is a congenital condition characterized in humans by the partial or complete absence of pigment in the skin, hair and eyes. Albinism is associated with a number of vision defects, such as photophobia, nystagmus, and amblyopia. The visual abnormalities regarding albinism are mainly caused by reduced melanin during optic development, leading to misrouting of optic nerve fibers and underdevelopment of the fovea. Lack of skin pigmentation makes for more susceptibility to sunburn and skin cancers. In rare cases such as Chédiak–Higashi syndrome, albinism may be associated with deficiencies in the transportation of melanin granules. This also affects essential granules present in immune cells, leading to increased susceptibility to infection.
Albinism results from inheritance of recessive gene alleles and is known to affect all vertebrates, including humans. Many genes are now known to cause oculocutaneous albinism, that include TYR, OSA2, TYRP1, SLC45A2, SLC24AB, and C10orf11, all of which affect both melanin synthesis and melanosome function. Unlike humans, other animals have multiple pigments and for these albinism is considered to be a hereditary condition characterised by the absence of melanin, in particular in the eyes, skin, hair, scales, feathers or cuticle. While an organism with complete absence of melanin is called an albino, an organism with only a diminished amount of melanin is described as leucistic or albinoid. The term is from the Latin albus, "white".
Signs and symptoms There are two principal types of albinism: oculocutaneous, affecting the eyes, skin and hair, and ocular, affecting the eyes only.
There are different types of oculocutaneous albinism depending on which gene has undergone mutation. With some there is no pigment at all. The other end of the spectrum of albinism is "a form of albinism called rufous oculocutaneous albinism, which usually affects dark-skinned people".
According to the US National Organization for Albinism and Hypopigmentation, "With ocular albinism, the color of the iris of the eye may vary from blue to green or even brown, and sometimes darkens with age. However, when an optometrist or ophthalmologist examines the eye by shining a light from the side of the eye, the light shines back through the iris since very little pigment is present." This specific phenomenon is known as iris transillumination. It occurs due to reduced pigment in the iris stroma and is a common clinical aspect in albinism
Because individuals with albinism have skin that entirely lacks the dark pigment melanin, which helps protect the skin from the sun's ultraviolet radiation, their skin can burn more easily from overexposure. People with albinism are typically advised to complete full skin examinations at least once a year to detect early skin cancer. They are also encouraged to follow sun protection measures that include regular application of sunscreen.
The human eye normally produces enough pigment to color the iris blue, green or brown and lend opacity to the eye. In photographs, those with albinism are more likely to demonstrate "red eye", due to the red of the retina being visible through the iris. Lack of pigment in the eyes also results in problems with vision, both related and unrelated to photosensitivity.
Those with albinism are generally as healthy as the rest of the population (but see related disorders below), with growth and development occurring as normal, and albinism by itself does not cause mortality, although the lack of pigment blocking ultraviolet radiation increases the risk of melanomas (skin cancers) and other problems such as actinic skin damage and long-term skin changes due to the sun, and studies show that without proper sun protection, cumulative exposure to ultraviolet light can significantly increase the risk of both non-melanoma skin cancers and melanoma, particularly in areas with strong sunlight.
Vision problems
Development of the optical system is highly dependent on the presence of melanin. For this reason, the reduction or absence of this pigment in people with albinism may lead to: Misrouting of the retinogeniculate projections, resulting in abnormal decussation (crossing) of optic nerve fibres Photophobia and decreased visual acuity due to light scattering within the eye (ocular straylight) Reduced visual acuity due to foveal hypoplasia and possibly light-induced retinal damage. Iris transillumination defects, which occur due to reduced pigment in the iris, allowing light to pass through the iris when viewed using slit-lamp retroillumination.
Eye conditions common in albinism include: Nystagmus, irregular rapid movement of the eyes back and forth, or in circular motion. Amblyopia, decrease in acuity of one or both eyes due to poor transmission to the brain, often due to other conditions such as strabismus. Optic nerve hypoplasia, underdevelopment of the optic nerve. Foveal Hypoplasia, incomplete development of the fovea, often a cause of reduced visual acuity in albinism. The improper development of the retinal pigment epithelium (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 discomfort in bright light, but this can be reduced by the use of sunglasses or brimmed hats.
Genetics
Oculocutaneous albinism is generally the result of the biological inheritance of genetically recessive alleles (genes) passed from both parents of an individual such as OCA1 and OCA2. Different OCA subtypes are caused by specific enzyme problems. OCA1 is due to a lack of the enzyme tyrosinase, resulting in no melanin production, while other types still allow partial enzyme activity and pigment production. A mutation in the human TRP-1 gene may result in the deregulation of melanocyte tyrosinase enzymes, a change that is hypothesized to promote brown versus black melanin synthesis, resulting in a third oculocutaneous albinism (OCA) genotype, "OCA3".
Molecular genetic testing has become the main method of confirming OCA subtype, as clinical features alone are often insufficient to distinguish between different genetic forms. Some rare forms are inherited from only one parent. There are other genetic mutations that are proven to be associated with albinism. All alterations, however, lead to changes in melanin production in the body.Online Mendelian Inheritance in Man, at Johns Hopkins University (See Online Mendelian Inheritance in Man for more information about this source).
The chance of offspring with albinism resulting from the pairing of an organism with albinism and one without albinism is low. However, because organisms (including humans) 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 sexes. An exception to this is ocular albinism, which it is passed on to offspring through X-linked inheritance. Thus ocular albinism occurs more frequently in males as they have a single X and Y chromosome, unlike females, whose genetics are characterized by two X chromosomes.
There are two different forms of albinism: a partial lack of the melanin is known as hypomelanism, or hypomelanosis, and the total absence of melanin is known as amelanism or amelanosis. Even within the same subtype, pigmentation levels can significantly vary, with some individuals producing small amounts of melanin, which results in a wide range of hypopigmentation rather than a complete absence of pigment.
Proximity to the Equator Individuals with oculocutaneous albinism residing in regions near the equator have a significantly increased risk of developing skin cancer called squamous cell carcinoma, a form of skin cancer that typically appears at a much earlier age than it does in most populations.
Enzyme The enzyme defect responsible for OCA1-type albinism is tyrosine 3-monooxygenase (tyrosinase), which synthesizes melanin from the amino acid tyrosine. Tyrosinase catalyzes the conversion of tyrosine into L-DOPA and then to dopaquinone, which is the major rate-limiting step in melanin production.
Evolutionary theories It is suggested that the early genus Homo (humans in the broader sense) started to evolve in East Africa around 3 million years ago. The dramatic phenotypic change from the ape-like Australopithecus to early Homo is hypothesized to have involved the extreme loss of body hair – except for areas most exposed to UV radiation, such as the head – to allow for more efficient thermoregulation in the early hunter-gatherers. The skin that would have been exposed upon general body hair loss in these early proto-humans would have most likely been non-pigmented, reflecting the pale skin underlying the hair of our chimpanzee relatives.
A positive advantage would have been conferred to early hominids inhabiting the African continent that were capable of producing darker skin – those who first expressed the eumelanin-producing MC1R allele – which protected them from harmful epithelium-damaging ultraviolet rays. Studies indicate that the evolution of dark skin in equatorial regions is closely associated with protection against folate breakdown caused by ultraviolet radiation, in addition to protection from DNA damage and the risk of skin cancer.
Over time, the advantage conferred to those with darker skin may have led to the prevalence of darker skin on the continent. The positive advantage, however, would have had to be strong enough so as to produce a significantly higher reproductive fitness in those who produced more melanin. The cause of a selective pressure strong enough to cause this shift is an area of much debate. Some hypotheses include the existence of significantly lower reproductive fitness in people with less melanin due to lethal skin cancer, lethal kidney disease due to excess vitamin D formation in the skin of people with less melanin, or simply natural selection due to mate preference and sexual selection.
When comparing the prevalence of albinism in Africa to its prevalence in other parts of the world, such as Europe and the United States, the potential evolutionary effects of skin cancer as a selective force due to its effect on these populations may not be insignificant. It would follow, then, that there would be stronger selective forces acting on albino individuals in Africa than on albinos in Europe and the US. In two separate studies in Nigeria, very few people with albinism appear to survive to old age. In regions with high ultraviolet radiation, people with albinism face higher risks of both severe sun damage and skin cancer, which reduces average life expectancy in affected populations without proper protection or access to medical care. One study found that 89% of people diagnosed with albinism are between 0 and 30 years of age, while the other found that 77% of albinos were under the age of 20.
It has also been theorized that albinism may have been able to spread in some Native American communities, because albino males were culturally revered and assumed as having divine origins. The very high incidence of albinism among the Hopi tribe has been frequently attributed to the privileged status of albino males in Hopi society, who were not required to perform physical work outdoors, shielding them from the harmful effects of UV radiation. This privileged status of albino males in Hopi society allowed them to reproduce with large numbers of non-albino women, spreading the genes that are associated with albinism.
Comorbidities Albinism can also be a feature alongside several syndromes: ABCD syndrome Albinism-hearing loss syndrome Chédiak–Higashi syndrome, in partial albinism Deafness, congenital, with total albinism Ermine phenotype in partial albinism Hermansky-Pudlak syndrome 1 to 11 (excluding 9)