Background
The term albinism originates from the word, albus (Latin for white), and it is an inherited disorder characterized by reduced pigmentation. [1] Albinism is caused by pathogenic variants in genes important for melanin synthesis. The phenotypic heterogeneity of albinism is associated with pathogenic variants in genes affecting different parts of the melanin pathway, and in such resulting in reduction at a different level of melanin production.
Clinical presentation and classification of albinism
This genetically heterogeneous disorder is characterized by hypopigmentation of the eyes, skin, and hair. Traditionally, albinism has been classified according to clinical phenotype, and the two main categories are oculocutaneous albinism (OCA) and ocular albinism (OA). Ocular involvement (decreased visual acuity secondary to foveal hypoplasia; misrouting of the optic nerves at the chiasm; photophobia and iris transillumination defects; nystagmus; and pigment deficiency in the peripheral retina) is significant in the disease presentation; thus, an ophthalmologist plays an important role in diagnosing this condition. [2] Albinism can present as a syndromic condition, such as Hermansky-Pudlak syndrome (HPS) or Chediak-Higashi syndrome (CHS), and this should not be forgotten as it has implications in patients care and management.
With advances in genetics, the classification of albinism has shifted emphasis by genotype as opposed to phenotype alone.
Pathophysiology
Melanin is a photoprotective pigment in the skin that absorbs ultraviolet (UV) light from the sun, thereby preventing skin and eye damage. With sun exposure, the skin normally tans as a result of increased melanin pigment in the skin. However, many albino individuals are sensitive to sunlight and can develop UV skin damage (ie, a sunburn) easily because of the lack of melanin. In addition to the skin, melanin is important to other areas of the body, such as the eyes and brain.
Melanin in the eye
The eye has 2 origins from which pigmented cells are derived: 1) the neuroectoderm of the primitive forebrain is the origin of melanocytes in the retinal pigment epithelium, iris epithelium (anterior and posterior), and ciliary epithelium (outer pigmented and inner nonpigmented) and 2) the neural crest is the origin of melanocytes in the iris stroma, ciliary stroma, and choroid (uveal melanocytes). Melanoblasts from the neural crest migrate to the skin, inner ear, and uveal tract.
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. Additionally, neural connections between the retina and the brain are altered if melanin in the retina is absent during development.
Melanin pathway
Melanin is formed in the melanosome organelle of the melanocyte (intracellular vesicles with the specific purpose of manufacturing and holding this pigment). Melanocytes are found in the skin, hair follicles, and pigmented tissues of the eye. Thus disruption in any part of the melanin synthesis pathway may affect part or all of these organs.
The melanin pathway consists of a series of reactions that converts tyrosine into 2 types of melanin: 1) black-brown eumelanin and 2) red-blond pheomelanin. Genetic variants affecting proteins/enzymes along this pathway inevitably result in reduced melanin production.
Tyrosinase is the major enzyme (coded on chromosome 11) involved in the series of conversions to form melanin from tyrosine. It is responsible for converting tyrosine to DOPA and then to dopaquinone. Through a sequence of steps, dopaquinone subsequently is converted to either eumelanin or pheomelanin.
Pathogenesis of ocular features
The development of the ocular system is highly dependent on the presence of melanin. Absent or decreased melanin can cause abnormal crisscrossing of optic nerve fibers as a result of misdirected retinogeniculate projections. Melanin is believed to control neuronal target specificity in the brain. In cases of incomplete pigmentation, the developing optic tracts almost entirely intersect at the chiasm, whereas in individuals without albinism, almost half (45%) of axons beginning in the temporal half of the retina pass through the chiasm uncrossed and project to the same-sided lateral geniculate nucleus. In individuals with healthy eyes, the majority of these fibers function in the central 20° of the temporal retina, but in those with albinism, almost all of the fibers crisscross at the chiasm and form a synapse in the opposite-sided lateral geniculate nucleus. This results in predominantly monocular vision and reduced binocular depth perception.
In addition to abnormal chiasmal decussation, albinism can produce a number of other visual symptoms and signs, including the following [6] :
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Reduced visual acuity (20/60 to 20/400) and color impairment
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Photophobia, due to light scattering within the eye
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High refractive errors
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Positive angle kappa
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Strabismus and related anomalous head tilt
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Congenital pendular nystagmus, starting at 2-3 months of age due to loss of visual function
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Iris hypopigmentation, and iris transillumination defects
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Fovea hypoplasia (absence of a fovea pit): it is the most significant factor causing decrease visual acuity
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Decrease retinal pigmentation
Epidemiology
Frequency
The incidence of albinism is 1 in 20,000 persons worldwide, compared with a rate of 1 in 37,000 in the United States. OCA1 is the most commonly found subtype in Caucasians, and accounting for 50% of all cases worldwide. OCA2 is responsible for 30% of cases worldwide and is more common in Africa. OCA3 affects 3% and OCA4 affects 17% of all cases globally.6 OCA5-8 are rare forms. HPS is a common type of albinism in Puerto Rico, but the disorder is rare in other parts of the world
Mortality/Morbidity
Albinism usually is not linked to mortality, and individuals with the disorder have a normal lifespan; the overall health of children and adults with albinism usually does not suffer from the decreased melanin in the hair, skin, and eyes, and this reduction causes no additional systemic effects. [7]
Normal growth and intellectual development should progress in a child with albinism, and they should accomplish developmental milestones on par with other children their age.
The bulk of morbidity linked to albinism is related to visual impairment, photosensitivity of the skin, and increased risk for cutaneous cancer.
Those with syndromes related to albinism, such as HPS or CHS, may experience hearing impairment or abnormal blood clotting. Individuals with albinism may have difficulty socially due to alienation because their appearance may differ from that of their families, peers, and others in their ethnic group.
Race
Individuals of all races can be affected by albinism, and it is common for parents of children with albinism to have eye and skin color typical of their ethnic background.
Sex
Albinism can occur in males and females alike; however, only males are affected in OA 1 (X-linked recessive OA), whereas females are carriers only.
Age
Albinism is always congenital.
Prognosis
Patients with albinism have a normal lifespan but there is an increased risk for skin cancer, and preventive measures are recommended for UV exposure. Genetic counseling is recommended for patients with albinism.
Patient Education
The main goals of patient education are to determine which type of albinism is present; to exclude systemic syndromes (eg, HPS, CHS); to avoid excess sun exposure; and to provide genetic counseling for the family.
Tables
Phenotype |
Gene |
location |
Inheritance |
OCA type 1A |
TYR |
11q14.3 |
AR |
OCA type 1B |
TYR |
11q14.3 |
AR |
OCA type 2 |
OCA2 |
15q12-q13.1 |
AR |
OCA type 3 |
TYRP1 |
9q23 |
AR |
OCA type 4 |
SLC45A2 (MATP) |
5p13.2 |
AR |
OCA type 5 |
OCA5 |
4q24 |
AR |
OCA type 6 |
SLC24A5 |
15q21.1 |
AR |
OCA type 7 |
LRMDA |
10q22.2-q22.3 |
AR |
OCA type 8 |
DCT |
13q32.1 |
AR |
OA type 1, Nettleship-falls |
GPR143 |
Xp22.2 |
XL |
