Albinism
- oculocutaneous albinism
Albinism is actually a group of several subtly different conditions
that have a hereditary error of melanin metabolism in common. Any
genetic abnormality of the melanin pigment system in which the synthesis
of melanin is reduced or absent can be called albinism. The reduction
in melanin synthesis can affect the skin, hair follicles, and eyes,
resulting in oculocutaneous albinism (OCA). If the skin and hair
are normally pigmented and just the eye pigmentation is affected,
the condition is called ocular albinism (OA).
There are two types of OCA, type I and type II. The classification
of oculocutaneous albinism depends upon the nature of the underlying
genetic defect. When a mutated tyrosinase gene produces inactive,
less active, or temperature-sensitive tyrosinase, its phenotype
is described as tyrosinase-negative (type I-A), yellow-mutant (type
I-B), or temperature-sensitive (type I-TS) OCA, respectively. Mutation
of the P gene encoding the tyrosine-transporting membrane protein
probably occurs in tyrosinase-positive OCA (type II).
Oculocutaneous albinism type I is an autosomal recessive disorder
characterized by absence of pigment in hair, skin, and eyes, and
does not vary with race or age. Severe nystagmus, photophobia, and
reduced visual acuity are common features. In contrast, the lack
of pigmentation does not obstruct the normal growth and development
of the skin or hair.
About 1 in 17,000 individuals in the United States have oculocutaneous
albinism, and more than 1 per cent of the population are heterozygous
for a gene producing albinism. The frequency varies with geographic
region. In British Columbia, the frequency of oculocutaneous type
I albinism is 1 in 67,800 and of type II albinism is 1 in 35,700.
In Northern Ireland the frequency of type I albinism is 1 in 10,000.
Famous albinos are believed to include Noah of flood fame and the
Rev. Dr. Spooner. Spooner was a brilliant classicist at Oxford University
whose amusing tendency to errors of speech came to be known as "spoonerisms".
Albinism was one of the first genetic diseases to be identified
in humans, but until quite recently little was known of the molecular
mechanisms involved in its pathogenesis. Recent advances have shown
us that mutations in at least seven separate genes can cause a reduction
in melanin pigment biosynthesis, producing the various associated
clinical features associated with albinism. However, there are at
least 37 different genetic mutations (more than one mutation can
occur in the same gene) defined that lead to OCA type I. There are
probably more that have yet to be identified. Some geneticists have
claimed there are over 60 different mutations. However, just 17
mutations account for over 90% of OCA type I affected individuals.
Albinism
- Griscelli syndrome
One form of partial albinism associated with immunodeficiency in
an individual is called Griscelli syndrome. This is a quite rare
disorder that involves a lack of pigment production and a variable
degree of immunodeficiency.
The common histopathology of Griscelli syndrome involves prominent,
mature melanosomes in skin and hair follicle melanocytes, but sparse
pigmentation of adjacent keratinocytes. This results in large, clumped
melanosomes in hair shafts and as a result the hair has a silvery-gray
sheen.
The associated immunodeficiency often involves impaired natural
killer cell activity, absent delayed-type hypersensitivity, and
a poor cell proliferation response to antigenic challenge. Occasionally,
impaired lymphocyte function and and in inability to produce normal
levels of immunoglobulins have also been described. The only treatment
approach with any success is a bone marrow transplantation from
a compatible donor. However, this has no effect on skin or hair
color.
Albinism
- references
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