Albinism Albinism is a heterogeneous condition inherited through either autosomal recessive or sex-linked recessive genes that affects approximately

1 in 17,000 people. Albinism is a defect of melanin production that results in little or no color (pigment) in the skin, hair and eyes. Melanin is a natural substances that gives color (pigment) to hair, skin, and the iris of the eye. It is produced by cells in the skin called melanocytes. The enzyme tyrosinase is missing from the melanocytes. Tyrosinase is a catalyst in the conversion of tyrosine to melanin. When the enzyme is missing no melanin is produced. Thus, it caused diseases albinism.

Simple flow chart to show to production of melanin from tyrosine.

There are 2 main types of albinism: i) Oculotaneous albinism ii) Ocular albinism. Oculotaneous albinism (OCA) describes a phenotype that lacks pigment in the skin, hair, and eyes. It is of 4 types- OCA1(OCA1A, OCA1B), OCA2, OCA3, OCA4. Ocular albinism occurs when the phenotype only lacks pigment from the eyes, the hair and skin appear normal in these individuals. Thus, oculotaneous albinism is typically more prominent. Oculocutaneous albinism type1 (OCA1) - It is tyrosinase - related albinism results from a genetic defect in an enzyme called tyrosinas. This enzyme helps the body to change amino acid tyrosine into the pigment. There are 2 subtypes of OCA1 (OCA1A and OCA1B): a) OCA1A - In OCA1A, the enzyme is inactive and no melanin is produced, leading to white hair and very light skin. b) OCA1B - In OCA1B, the enzyme is minimally active and small amount of melanin is produced, leading to hair that may darken to blonde, yellow/ orange or even light brown, as well as slightly more pigment in the skin. Oculocutaneous albinism type2 (OCA2) - it is a P-gene albinism results from a genetic defect in the p-protein that helps the tyrosinase enzyme to function. Individuals with OCA2 make a minimal amount of melanin pigment and can have hair color ranging from very light blonde to brown.

Oculocutaneous albinism type3 (OCA3) - It is rarely desribed and results from a genetic defect in TYPR1, a protein related to tyrosinase. Individuals with OCA3 can have substantial pigment. Oculocutaneous albinism type4 (OCA4) - It results from a genetic defect in the SLC45A2 protein that helps the tyrosinase enzyme to function. Individuals with OCA4 make a minimal amount of melanin pigment similar to persons with OCA2. Ocular albinism (OA1) - It is caused by a change in the GPR143 gene that plays a signalling role that is especially important to pigmentation in the eye. OA1 follows a simpler pattern of inheritance because the gene for OA1 is on X chromosome. Female has 2 copies of X chromosomes while males have only 1 copy (another Y chromosome). To have Ocular albinism, a male only need to inherit one changed copy of the gene for ocular albinism from his carrier mother. Therefore almost all the people with OA1 are males.

Example showed that albinism is caused by sex-linked recessive gene.

The Biochemical Pathway That Is Affected By Albinism

Melanin synthesis starts with the amino acid tyrosine, which is oxidized to dihydroxyphenylalanine (DOPA) by the enzyme tyrosinase. DOPA is then oxidized to dopaquinone by the same enzyme. Dopaquinone is spontaneously transformed to leucodopachrome, and then to dopachrome. The latter is decarboxylated to 5,6-dihydroxyindole, and then oxidized to indole 5,6-quinone. Indole-quinone is converted to melachrome, and then polymerizes to eumelanin (pigment with brown to black color). Dopaquinone can react with cysteine under high concentrations of the latter to form cysteinyl-dopa, which is oxidized to pheomelanin (yellow to red color pigment). DOPA can also react with glutathione to form pheomelanin (brown to black pigment). When the absence of enzyme tyrosinase, it prevent the synthesis of melanin pigment by melanocytes. Symptoms Most oculocutaenous albinistic humans appear white or very pale as the melanin pigments responsible for brown, black, and some yellow colorations are not present. Ocular albinism results in pale blue eyes, and may require genetic testing to diagnose. Individuals with albinism have skin that partially or entirely lacks the dark pigment melanin, which helps protect the skin from the sun's ultraviolet radiation, their skin can burn more easily from overexposure and increase the risk of skin cancer The human eye normally produces enough pigment to color the iris blue and lend opacity to the eye. However, there are cases in which the eyes of an albinistic person appear red or purple, depending on the amount of pigment present, due to the red of retina being visible through the iris. Lack of pigment in the eyes also results in problems with vision, both related and unrelated to photosensitivity. The albinistic are generally as healthy as the rest of the population, with growth and development occurring as normal, and albinism by itself does not cause mortality. Visual problems Development of the optical system is highly dependent on the presence of melanin, and the reduction or absence of this pigment in albinistic individuals may lead to:

Decussation (crossing) - Misrouting of the retinogeniculate projections, resulting in abnormal of optic nerve fibres. Photophobia - decreased visual acuity due to light scattering within the eye (ocular straylight). Foveal Hypolasia - Reduced visual acuity and possibly light-induced retinal damage 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. - muscle imbalance of the eyes "crossed eyes" (esotreopia), "lazy eye" or an eye that deviates out (exotropia).

Optic nerve hypoplasia - underdevelopment of the optic nerve where the nerve signals from the retina to the brain does not follow the usual routes.

Diagnosis a) Chorionic Villus Sampling (CVS) A chorionic villus sampling (CVS) test during the fifth week of pregnancy may also reveal some types of albinism. But, chorionic villus sampling is not recommended for women who have vaginal bleeding or spotting during the pregnancy. It is not typically recommended for women who have Rh sensitization from a previous pregnancy. Overall, this prenatal testing procedure involves taking a sample of the chorion frondosumthat part of the chorionic membrane containing the villifor laboratory analysis. The chorionic membrane is the outer sac which surrounds the developing fetus. Chorionic villi are microscopic, finger-like projections that emerge from the chorionic membrane and eventually form the placenta. The cells that make up the chorionic villi are of fetal origin so laboratory analysis can identify any genetic, chromosomal, or biochemical diseases of the fetus. b) Hairbulb Pigmentation Test Hairbulb pigmentation test is used to identify carriers by incubating a piece of the person's hair in a solution of tyrosine, a substance in food which the body uses to make melanin. If the hair turns dark, it means the hair is making melanin (a "positive" test); light hair means there is no melanin. This test is the source of the names of two types of albinism: "ty-pos" and "ty-neg." c) Tyrosinase Test The tyrosinase test is more precise than the hairbulb pigmentation test. It measures the rate at which hair converts tyrosine into another chemical (DOPA), which is then made into pigment. In hair, tyrosine converts with the help of "tyrosinase." In some types of albinism, tyrosinase doesn't do its job, and melanin production breaks down. Treatment There is no treatment that can replace the lack of melanin that causes the symptoms of albinism. Doctors can only treat eye problems that often accompany the lack of skin color. 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. 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. Glasses and other vision aids, large-print materials 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 (with a strong reading lens), prescription reading glasses, and/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. Some use 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. Help The National Organization for Albinism and Hypopigmentation (NOAH) PO Box 959, East Hampstead, NH 03826-0959 Phone: 800437-2310 (US&Canada) Phone: 608887-2310 Fax: 800-648-2310 http://www.albinism.org The Kiwanis Disability Information and Support Centre (KDISC) Phone: 6(012)2100679 (Adeline) / 6(019)6638288 (Sew Chin) info@disabilitymalaysia.com References 1. Elias I. Traboulsi, W. Richard Green.(2006). An Overview of Albinism and Its Visual System Manifestations (Chapter 38, Volume 4). Lippincott Williams & Wilkins. 2. Retrieved from website http://www.elmhurst.edu/~chm/vchembook/635pku.html 3. Retrieved from website http://medical-dictionary.thefreedictionary.com/Albino+people 4. Retrieved from website http://medicaldictionary.thefreedictionary.com/Chorionic+Villus+Sampling 5. Retrieved from website http://powerofthegene.com/joomla/index.php/geneticallyinherited-diseases/dermatological-disorders/oculocutaneous-albinism

Universiti Pendidikan Sultan Idris Faculty Science and Mathematics Department of Biology Semester 2 Session 2011/2012 SBK3013 Biochemistry

Albinism

Name Matric No Course Lecturer

: Phua Wan Jien : D20091035127 : AT16 : Dr Rosmilah Binti Misnan