Albinism is of a group of inherited disorders characterized by a congenital reduction or absence of melanin pigment due to defective production of melanin from tyrosine.
An estimated 1 in 17,000 people have one of the types of albinism.
Oculocutaneous albinism is the most common type of albinism
Both males and females can be affected.
Classification of albinism
Two main categories are
- Oculocutaneous albinism (OCA)
- Ocular albinism (OA).
This is traditional phenotypical classification. With understanding of mutations, genotypes have been added and are discussed below.
Oculocutaneous albinism 1
OCA 1 is results from mutations to the tyrosinase gene found on chromosome 11 (band 11q14-21).
There is the presence of marked hypopigmentation at birth and is distinguishing feature of OCA 1. Most individuals have white hair, milky white skin, and blue irides at birth. The irides can be very light blue and translucent, and may appear pink or red in ambient or bright light.
With age, the irides usually become darker blue and may remain translucent or lightly pigmented.
Oculocutaneous albinism 1A
- Classic tyrosinase-negative oculocutaneous albinism
- Most severe form of oculocutaneous albinism
- Mutations of the tyrosinase gene on chromosome 11 lead to produce completely inactive tyrosinase, resulting in no melanin formation
- White hair and skin, with blue and translucent irides.
- No pigmented lesions develop in the skin
- Amelanotic nevi may be present
- No tanning potential due to lack of melanin
- At risk for sunburn and skin cancer.
- Eye involvement
- Decreased visual acuity [
- Nystagmus tend to be the worst in this subtype.
- Hair bulb incubation in tyrosinase is usually negative.
Oculocutaneous albinism 1B
- Mutations of the tyrosinase gene resulting in decreased/residual enzyme activity.
- Pigmentation rangs from little cutaneous pigment to nearly normal.
- Completely lack pigment at birth [similar to OCA1]
- Increase in skin, hair, and eye pigment with age
- May tan with sun exposure.
- Visual acuity may improve with age.
- Hair bulb testing shows greatly reduced activity of tyrosinase
- Subtype of OCA 1B caused by a mutation that produces a temperature-sensitive tyrosinase enzyme.
- The enzyme does functions in cooler areas of the body (arms and legs) but not at regular body temperatures (axillary and scalp region)
- The body, arm and leg hair pigment is usually dark, while axillary and scalp hair remains white
- May appear similar to OCA1A at birth because temperature of the fetus is high resulting in absent pigment.
Oculocutaneous albinism 2
- Classic tyrosine-positive OCA
- Most prevalent type of albinism in all races.
- Autosomal recessive
- Mutation different from OCA1 (band 15q11-13), affects the gene coding for the P protein
- Encodes for a melanosomal membrane protein involved in the transport of tyrosine.
- Tyrosinase is normal
The phenotypic spectrum of OCA 2 arnges from from absent pigmentation to almost normal pigmentation.
Oculocutaneous albinism 3
- Previously known as red/rufous albinism
- Mutation to the human gene coding for TRP-1.
- TRP-1 acts as a regulatory protein in the production of black melanin (eumelanin
- Autosomal recessive
- The ocular features are not fully consistent with the diagnosis of OCA
- Optic nerve development is normal.
Ocular albinism 1
- X-linked recessive [Nettleshop-Falls type]
- Locus is Xp22.
- OA1 gene is a glycoprotein thought to be necessary for the maturation of melanosomes
- Males manifest the disease and females are carriers
- Normal skin but usually paler than first-degree relatives
- Involves the eyes only
- Decreased visual acuity
- Refractive error
- Fundus hypopigmentation
- Absent foveal reflex
- Iris translucency
- Posterior embryotoxon
- 30% of patients
- Implies anterior segment dysgenesis
- Skin biopsy in carriers and in individuals with OA 1 usually shows the presence of macromelanosomes.
Pathophysiology of Albinism
Melanin is a pigment in the skin that absorbs ultraviolet light from the sun, thereby preventing skin damage. The tanning of the skin normally on sun exposure is due to increased melanin pigment in the skin.
Many persons with albinism are sensitive to sunlight and develop a sunburn because of the lack of melanin.
Melanin is also important to other areas of the body, such as the eyes and brain, although the function in these areas is not currently known.
The presence of melanin during ocular development is important. The fovea fails to develop properly if melanin is absent during development. Other areas of the retina develop normally regardless of the presence of melanin. An absent melanin during development may cause altered neural connections between the retina and the brain.
The amount of pigment necessary for appropriate ocular development is currently unknown. If melanin is absent or reduced, the ocular features appear
Melanin is formed in the melanosome organelle of the melanocyte. Melanocytes are found in the skin, hair follicles, and pigmented tissues of the eye. The melanin pathway consists of a series of reactions that converts tyrosine into 2 types of melanin.
Tyrosinase is the major enzyme (coded on chromosome 11) involved in the series of conversions to form melanin from tyrosine
Finally, P protein is a melanosomal membrane protein that is believed to be involved in the transport of tyrosine prior to melanin synthesis. Mutation to this P gene produces OCA 2.
Severe forms are easier to recognize whereas those with mild disease or ocular features only are difficult to diagnose.
Apart from skin features, patients may report decreased central vision and photophobia. Skin symptoms include skin photosensitivity.
Inquire about a family history of albinism. Children with albinism tend to prefer reading with a head tilt and usually hold reading material up close.
After checking hair and skin color for depigmentation, patients should be examined for eyes..
The ocular features common to all types of albinism include the following:
- Refractive error and astigmatism
- Iris depigmentation and iris transillumination
- Fovea hypoplasia
- Reduced depth perception
- A positive angle kappa [related to the anomalous decussation of optic axons]
Albinism does not cause a delay in development or mental retardation. If these features are present, other causes should be suspected.
Ascertaining type of Albinism
- Assess the phenotype.
- If OCA 1A is suspected,
- Hair bulb assay may
- negative result indicates OCA 1A
- Positive result could indicate OCA 1B, OCA 2, OCA 3, or OA 1.
- Genetic analysis.
- Skin biopsy in OA 1 shows the presence of macromelanosomes.
Hair bulb assays
Indicate the status of tyrosinase activity
Hair bulbs are taken from the scalp, and the catalytic activity of tyrosinase is determined. The usefulness of this test is debatable because a negative result indicates oculocutaneous albinism 1A, but a positive result still leaves the possibility of OCA 1, OCA 2, OCA 3, or OA 1.
Genetic Sequence Analysis
The most definitive test in determining the albinism type is genetic sequence analysis. Of course, the test is useful only for families with individuals who have albinism. The test cannot be used as a screening tool.
Genetic sequence analysis can be used to determine if a fetus has albinism.
Macular optical coherence tomography
To classify foveal abnormalities and help determine the cause of the infantile nystagmus with the use of foveal morphology.
Visual-evoked potential tests
Sweep visual-evoked potential testing can be used as a predictive tool for recognition acuity in children with albinism.
There is no potential effective treatment or cure existed for albinism, but the following may be helpful
- Low-vision aids.
- Tinted glasses may be used to reduce photophobia.
- Treatment of strabismus
- Nitisinone elevates plasma tyrosine levels and increases eye and hair pigmentation. Nitisinone may soon be a potential treatment for people with ocular albinism.
- Skin cancer, sunburn
- Reduced visual acuity
- Social stigma
Patients with albinism have a normal lifespan.
An increased risk of skin cancer exists; however, this is curable.
Patients may have children with no complications. Whether or not their children have albinism depends on the genetic makeup of their partner.
Albinism does not cause a delay in development or mental retardation.
Excess sun exposure should be avoided.