Albinism

Albinism is a genetic deficiency of melanin pigment production. Production is rarely totally absent but perhaps 1 to 10% of normal. It is an inherited condition, usually as an autosomal recessive but some forms are X-linked. The OMIM link at the end shows the result of a search for "albinism". A number of different chromosomes are involved, depending upon the type.

Oculo-cutaneous albinism (OCA) affects the eyes, hair and skin, whereas only the eyes are affected in ocular albinism (OA).

Approximately one in 17,000 people have one of the types of albinism. A study from Bradford found that the incidence of visual impairment in children was disproportionately high in those of Pakistani origin.¹ Albinism was just one of the causes of visual impairment with congenital nystagmus being commoner. The higher incidence amongst the Pakistani community was attributed, at least in part, to the high incidence of consanguineous marriages.

About 1 in 70 people carries a gene for OCA. Albinism can affect all races and has been extensively studied in other species like the mouse.

Symptoms

Visual problems are an important feature of albinism.² Melanin is reduced or absent where it is normally present, in the eye, skin, hair and brain and this causes maldevelopment of neural pathways³ related to vision. Severe nystagmus, photophobia, strabismus and reduced visual acuity are common features..

Signs

The precise appearance depends upon which syndrome or condition is involved.
Popular opinion is that people with albinism have red eyes, but the colour of the iris varies from a dull grey to blue to brown. A brown iris is common in ethnic groups with darker pigmentation. Under certain lighting conditions, there is a reddish or violet hue reflected through the iris from the retina, similar to that which occurs when a flash photograph is taken of a person looking directly at the camera, and the eyes appear red. With some types of albinism the red colour can reflect back through the iris as well as through the pupil.

• Oculocutaneous albinism type I: This is an autosomal recessive disorder caused by mutation in the tyrosinase gene on chromosome 11. Patients have no pigment in hair, skin, and eyes, and the condition does not vary with race or age.
• Oculocutaneous albinism type IA (OCA1A): Such patients do not make any melanin in their skin, hair or eyes, because they have no active tyrosinase. They are born with white hair and skin and blue eyes, and there is no change as they mature into teenagers and adults.. The phenotype is the same in all ethnic groups around the world and at all ages. With time, the hair may develop a dense rather than a translucent white or a slight yellow tint. The iris is translucent and appears pink early in life and often turn a grey-blue colour with time. No pigmented lesions develop in the skin, although amelanotic naevi can be present. Visual acuity is so poor they are classified as blind. Vision does not improve with age.
• Oculocutaneous albinism type IB (OCA1B): These patients have some tyrosinase activity. Patients have very little or no pigment present at birth but develop varying amounts of melanin in the hair and the skin in the first or second decade. This varies from very little to nearly normal skin and hair pigment. Ethnic and family pigment patterns influence the pigmentation. Sun exposure may cause some tanning of the skin but it is more common to burn. Near normal cutaneous pigmentation can lead to confusion with ocular albinism and the hair can develop a golden colour ("yellow albinism"). Very few freckles develop. Eyelash pigment is often darker than that of the scalp hair. Visual acuity is very poor but may improve with age. Subtypes of OCA1B represent different mutations:
  • Minimal pigment OCA (platinum OCA): There is white skin and hair, blue irides with no pigment at birth. There is an increase in iris pigment over first decade.
  • Temperature-sensitive OCA: This type of mutation of the tyrosinase gene produces an enzyme that does not work at central body temperature as on the scalp and under the arms but it does work in cooler parts of the body such as the arms and legs, to produce pigmentation in these areas.
• Tyrosinase-positive oculocutaneous albinism (OCA, type II): It is the most prevalent type of albinism in the world, primarily because of the high frequency in equatorial Africa (1:1,100 in parts of Nigeria). It is an autosomal recessive disorder with mutation on chromosome 15. Pigment is present in the hair and iris at birth or early in life. Skin pigment can develop in sun exposed regions of the skin, but tanning is usually absent. In Caucasian individuals the amount of pigment present at birth varies from minimal to moderate. The hair is yellow at birth and remains yellow through life, although the colour may turn darker and may turn grey with age. The skin is white at birth with little change over time, and no tan develops.
• Oculocutaneous albinism (type III): It is caused by an autosomal recessive mutation in tyrosinase-related protein-1 gene on chromosome 9. It is also known as "Brown OCA". This is a type of albinism that is recognized only in the Afro-Caribbean populations, especially in Puerto Rico. The hair and skin colour are light brown, freckled skin and reddish hair may be present, and the iris is grey to tan at birth. Affected individuals are primarily recognized as having albinism because they have all of the ocular features of albinism. The iris has punctate and radial translucency, and moderate retinal pigment is present. The skin may darken with sun exposure.
• Ocular albinism: It involves the eyes only. Skin colour is usually normal or slightly lighter than the skin of other family members. Eye colour may be in the normal range, but there is no pigment in the retina. Subtypes are:
  • Ocular Albinism Type 1 (OA1): This is an X-linked ocular albinism and so affects predominantly males. There is the Albino red pupillary reflex with depigmented fundus and prominent choroidal vessels, nystagmus, photophobia and impaired vision with normal skin pigmentation. Carrier females have a mosaic fundal pigmentation.
  • Ocular Albinism Type 2 (OA2): This is also an X-linked ocular albinism. There is an albino fundus with foveal hypoplasia, marked visual impairment, nystagmus, myopia, astigmatism and colour blindness. Female carriers may have abnormal colour vision.
  • Autosomal recessive ocular albinism: The mutation is on chromosome 6. Features are similar to males with X-linked ocular albinism.

The hair is blond but not completely white. The iris is grey. The pupils are red due to reflection of the flashlight back from the retina. This is a common finding in normal subjects with flash photography when there is a dilated pupil and it is called "red-eye". It is commoner with albinism. Light is reflected from the centre of the left pupil but above and medial to the centre on the right. This may suggest strabismus.

Diagnosis is based on careful history of pigment development and an examination of the skin, hair and eyes. The only type of albinism that has white hair at birth is OCA1.

Hair bulbs, plucked from the scalp can be used to assess tyrosinase activity. The catalytic activity of tyrosinase is determined either by incubation in DOPA and the production of melanin, assessed by visual inspection or by a radioactive biochemical assay in which the samples are incubated with a radiolabeled tyrosine precursor and the amount of radiolabel released after enzymatic conversion quantified spectrophotometrically. The value of this test is debatable since a negative result indicates OCA 1A, but a positive result still leaves the possibility of OCA 1, OCA 2, OCA 3, or OA 1.

The most accurate test for determining the specific type of albinism is a genetic test. The test is useful only for families that contain individuals with albinism, and cannot be performed practically as a screening test for the general population. None of the tests available is capable of detecting all of the mutations of the genes that cause albinism, and responsible mutations cannot be detected in a small number of individuals and families with albinism.

• There is an association between OCA2 and the hypopigmentation found with Prader-Willi syndrome and Angelman Syndrome. Many individuals with Prader-Willi syndrome are hypopigmented but most do not have the typical ocular features of albinism.
• The Hermansky-Pudlak Syndrome includes OCA and the accumulation of a material called ceroid in tissues throughout the body. HPS is very rare, except in Puerto Rico where it is approximately 1in1,800. The most important medical problems in HPS are related to interstitial lung fibrosis, granulomatous colitis and mild bleeding problems due to a deficiency of granules in the platelets
• The Chediak-Higashi Syndrome is a rare syndrome that includes an increased susceptibility to bacterial infections, hypopigmentation, and the presence of giant granules in white blood cells. The skin, hair, and eye pigment is reduced or diluted in CHS.

Eye Problems:

• Ophthalmologists and optometrists can help people with albinism compensate for their eye problems, but they cannot cure them. Extreme far-sightedness or near-sightedness and astigmatism are common. Corrected visual acuity ranges from 6/6 to 6/120, legally blind. Normal or near-normal vision is unusual even with glasses. Young children may simply need glasses, and older children can sometimes benefit from bifocal glasses. Low vision clinics may prescribe telescopic lenses mounted on glasses, sometimes called bioptics, for close-up work as well as for distant vision. Recently smaller and lighter telescopes have been developed. However, ordinary glasses or bifocals with a strong reading correction may serve well for many people with albinism.
• For photophobia dark glasses or photochromic lenses are used. There is no proof that dark glasses will improve vision, even when used at a very early age, but they may improve comfort. Many children and adults with albinism do not like tinted lenses, and benefit more from wearing a cap or a visor when outdoors in the sun.

Help at school

Most children with albinism should function in a mainstream classroom environment, provided the school gives specific attention to their special needs for vision. Preschool evaluations allow parents and teachers to form an Individual Education Plan for the child. Braille is unnecessary and children with albinism will read the dots visually.
Various classroom aids help children with albinism:

• High contrast written material: Children with albinism have difficulty reading worksheets and papers that are light or low contrast. Black on white high contrast material is better.
• Large-type textbooks: The school can usually obtain large type editions from the publishers of their regular textbooks. Because children with albinism often have difficulty keeping track of their place on the page while shifting back and forth between a textbook and a worksheet, it may help to allow them to write in the textbook. Worksheets may need to be copied on a machine that enlarges print size. Children with albinism do not always need large-type materials, however, and large type should not be a substitute for optical visual aids. Use of audio tapes may be preferable to voluminous reading.
• Copies of the teacher's board notes: The child with low vision can read the notes close-up while classmates read the board.
• Various optical devices: Hand-held monoculars, telescopic lenses mounted over eye glasses, video enlargement machines (closed circuit TV), and other types of magnifiers may help some people with albinism.
• Computers: Children with albinism should begin key-boarding skills early, since computers with software for large character screen display can help greatly with writing projects.

Drugs

They are very susceptible to burning and subsequent skin malignancies. High factor sun protection cream and avoidance of sunlight are essential.

Surgical:

• For nystagmus eye muscle surgery can reduce the movement of the eyes. However, vision may not improve in all cases due to other associated eye abnormalities. People with albinism may find ways of reducing nystagmus while reading, such as placing a finger by the eye, or tilting the head at an angle where nystagmus is dampened.
• For strabismus, ophthalmologists prefer to treat infants starting at about six months age, before the function of their eyes has developed fully. They may recommend a patch over one eye to promote the use of the non-preferred eye. In other cases, the alignment of the eyes improves with the wearing of glasses. Correction of strabismus by surgery or by injection into the extraocular muscles does not completely correct the problem with both eyes fixing on one point. Although these treatments may improve the alignment of the eyes and enhance psycho-social development and interpersonal interactions, they cannot correct the improper routing of the neural pathways. Depth perception is not improved with eye muscle surgery.

Protection from the sun is essential to prevent burning and cutaneous malignancies including basal cell carcinoma, squamous cell carcinoma and malignant melanoma. This is particularly important in Africa⁴ or other places where the sun is very strong but should not be forgotten in temperate climate. Otherwise, life expectancy is normal.
Albinism may cause social problems, because people with albinism look different from their families, peers, and other members of their ethnic group. In some parts of Africa it is associated with social stigma, myth and superstition.²

Growth, development and intellectual development in the child are normal. Vision is invariably severely impaired.

Gene testing can be used to determine if a fetus has albinism. Amniocentesis is performed at 16 to 18 weeks gestation. Those considering such testing should be aware that given proper support, children with albinism can function well despite considerable visual handicap and have a normal life span.