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Albinism
ALBINO
Albinism is a disorder of amino acid metabolism that results in a congenital hypopigmentation of ocular and systemic tissues. Cellular pigmentation is dependant upon a cell’s ability to manufacture and sequester the pigment melanin. This is accomplished within organelles called melanosomes which reside inside cells called melanocytes.
PathophysiologyMelanin is the pigment responsible for skin, hair, and
eye coloration. Albinism is caused by a disorder of melanin
metabolism, and the defect can lie with either melanin synthesis or distribution. Melanin is synthesized in melanocytes from the amino acid tyrosine. This process takes place in special organelles called melanosomes.
Oculocutaneous albinism involves a reduction in the amount of melanin present in each of the melanosomes.
Ocular albinism is a reduction in the number of melanosomes, although each melanosome may be fully pigmented.
Type I oculocutaneous albinism, which is characterized by complete absence of skin and eye pigmentation, despite a normal number of melanosomes.
Type II (tyrosine positive) oculocutaneous albinism defect is within the P polypeptide, which is a melanosomal tyrosine transporter. The P gene has been mapped to chromosome 15 and is more commonly linked with albinism in patients of African descent.
Ocular albinism type I is an X-linked disorder related to defects in the OA1 gene. This gene produces pigment cell-specific, intracellular G-protein coupled receptor (GPCR), which appears to result in faulty transport of melanosomes and lysosomes as well as macromelanosomes.
Visual problemsEye conditions common in albinism include:
Nystagmus, Irregular rapid movement of the eyes back and forth, or in circular motion.
Refractive errors such as myopia or hyperopia and especially astigmatism
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.
Photophobiais a symptom of abnormal intolerance to
visual perception of light.
Astigmatism (eye)is an optical defect in which vision is blurred
due to the inability of the optics of the eye to focus a point object into a sharp focused image on the retina.
GeneticsEach type of albinism is caused by genetic mutations.
OCA types 1, 2, 3 and 4 are all inherited as autosomal recessive traits (they are not located on sex chromosomes and must be present in both gene copies to be inherited). These four types of OCA result from mutations to the TYR, OCA2, TYRP1, and SLC45A2 genes, respectively.
The four types of OCA, OA is a sex-linked trait, caused by a mutation to the X chromosome. CHS, HPS, and GS are all autosomal recessive, caused by mutation to the LYST, HPS, and RAB27A genes. LYST affects the Golgi body’s functionality (which is crucial to melanosome production), while HPS and RAB27A affect protein synthesis.
DiagnosisIn assessing the phenotype of the patient, if the
newborn, and especially the adult, completely lacks pigment in the skin and hair, the individual probably has OCA 1A. If minimal pigment is apparent, the individual could be classified as either OCA 1B, OCA 2, or OCA 3.
If the individual has silvery colored hair and neutrophils with large inclusions, as observed by light microscopy of a blood smear, the diagnosis would be Chediak–Higashi syndrome.
If the individual has moderate to minimal hypopigmentation and exhibits reduced blood clotting upon testing, the diagnosis would be Hermansky–Pudlak syndrome.
A hair bulb assay could be performed to identify OCA 1A more definitely. In this test, hair bulbs are plucked from the scalp and the catalytic activity of tyrosinase is determined either (a) by a histochemical procedure in which the
samples are incubated in the substrate DOPA and the consequential induction of melanin determined by visual inspection.
(b) by a radioactive biochemical assay in which the samples are incubated with a radiolabelled tyrosine precursor and the amount of radiolabel released after enzymatic conversion quantified spectrophotometrically. A negative result with either assay indicates OCA 1A, a positive result indicates OCA 1B, OCA 2, or OCA 3. OA 1 will also be positive.
To differentiate between OCA 1B, OCA 2, OCA 3, sequence analysis of the genes encoding tyrosinase, P protein, and TRP-1, respectively, must be performed.
Alternatively, a 5–8 mm shave skin biopsy can be obtained from the patient. Cultures of melanocytes can be established in order to assess the expression and/or function of tyrosinase, P protein, and TRP-1.
If X linked ocular albinism (OA 1) is suspected after examining the ocular phenotype, female family members need to be assessed for the presence of a mud splattered fundus, indicating carrier status. A skin biopsy can be sent to a histology laboratory to look for macromelanosomes in the epidermis.
TreatmentFor the most part, treatment of the eye
conditions consists of visual rehabilitation. Surgery is possible on the ocular muscles to decrease nystagmus, strabismus and common refractive errors like astigmatism.
Strabismus surgery may improve the appearance of the eyes.
Nystagmus-damping surgery can also be performed, to reduce the "shaking" of the eyes back and forth.
The effectiveness of all these procedures varies greatly and depends on individual circumstances. More importantly, since surgery will not restore a normal RPE or foveae, surgery will not provide fine binocular vision.[ In the case of esotropia (the "crossed eyes" form of strabismus), surgery may help vision by expanding the visual field .
Bioptics, glasses which have small telescopes mounted on, in, or behind their regular lenses, so that they can look through either the regular lens or the telescope.
Glasses and other vision aids, large-print materials and CCTV, as well as bright but angled reading lights, can help individuals with albinism, even though their vision cannot be corrected completely. Some people with Albinism do well using bifocals, prescription reading glasses or hand-held devices such as magnifiers or monoculars.
Contact lenses may be colored to block light transmission through the iris. But in case of nystagmus this is not possible, due to the irritation that is caused by the movement of the eyes.
Magnifiers or Monoculars
Bioptics
Epidemiology
Albinism affects people of all ethnic backgrounds; its frequency worldwide is estimated to be approximately one in 17,000. Prevalence of the different forms of albinism varies considerably by population, and is highest overall in people of sub-Saharan African descent.
Two principal types of albinism:Oculocutaneous- incomplete melanization of the
cellular melanosomes.Tyrosinase-positive oculocutaneous albinism
An activity is normal but there is an inability of the cells to sequester the synthesized melanin into the melansomes.
Tyrosinase-negative oculocutaneous albinismA congenital inactivity of the enzyme tyrosinase
that prevents the cell use of tyrosine formation of the pigment melanin.
Ocular exhibits pigmentary dilution due to abnormalities in melanosome synthesis rather than inadequate melanization.
Ocular albinism (OA)
Oculocutaneous albinism (OCA)
•OCA 1A• OCA 1A is the most severe form of OCA. Tyrosinase activity is completely absent and there is no melanin in the skin or eyes. Visual acuity is decreased to 20/400. Nonsense, frameshift, and missense mutations account for OCA 1A. The gene position is on chromosome 11 (11q14-21).
•OCA 1B•has a greatly diminished, but not absent, level of tyrosinase. OCA 1B individuals may exhibit an increase in skin, hair, and eye pigment with age and do tan with sun exposure. Fifty five mutations of the tyrosinase (TYR) gene have been found to date.
Oculocutaneous albinism type 1OCA1A OCA1B
•OCA 2•Patients with OCA 2 were formerly referred to as “tyrosinase positive” oculocutaneous albinos because the mutation causing OCA 2 does not affect the tyrosinase gene, instead affecting the Ppolypeptide. •The disease is also autosomal recessive, but coded on a different chromosome from OCA 1—that is, 15q11-13.
•Oculocutaneous albinism type 3 OCA 3 is caused by a defect in tyrosine related protein 1 (TRP-1).TRP-1 is the product of the brown locus in the mouse. A mutant allele in the mouse at that position causes the fur to be brown rather than black. The human gene coding for TRP-1 is on the short arm of chromosome 9 (9p23). •The phenotypic features of OCA 3 in black patients are light brown hair, light brown skin, blue/brown irides, nystagmus, and diminished visual acuity
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