Information on the following diseases can be found in the Related Disorders section of this report:

• Menkes Disease

Albinism is a group of rare inherited syndromes characterized by the absence of color (pigmentation) in the skin, hair and eyes. In Oculocutaneous Albinism, the skin and the eyes are generally white. The symptoms of Tyrosinase-Negative and Tyrosinase-positive forms of Albinism are similar at birth. In both forms newborns typically have pinkish-white skin, white hair and pink, light gray, blue or hazel eyes. Those children who are tyrosinase- positive will eventually develop pigmentation in the skin, hair, and eyes as they grow older. Those who have Tyrosine-negative Albinism will not develop color in their skin, hair or eyes. Children with both forms of Oculocutaneous Albinism may experience involuntary rhythmic movements of the eyes (nystagmus), distorted vision due to an irregular cornea (astigmatism), crossed eyes (strabismus) and/or nearsightedness (myopia). Children may also experience an abnormal sensitivity to light (photophobia). Squamous cell carcinomas (a type of skin cancer) may develop in children with Oculocutaneous Albinism.

Another form of Oculocutaneous Albinism known as Albinoidism or Partial Albinism has been described. This form of Albinism is characterized by a lack of color in the skin (hypomelanism), hair and certain pigmentation abnormalities of the eye. Generally other visual defects do not occur.

In Ocular Albinism, the skin and hair are relatively normal but are quite fair. Heightened sensitivity to light (photophobia) and the visual abnormalities of Oculocutaneous Albinism are typically present. There may be patchy degeneration of the retina (retinal mosaicism) in the eyes.

The different syndromes of Oculocutaneous Albinism have distinctive characteristics and symptoms. Hermansky-Pudlak Syndrome and Chediak-Higashi Syndrome are two different syndromes of Oculocutaneous Albinism that are characterized by a loss of pigment. Other symptoms of Hermansky-Pudlak Syndrome may include abnormalities of fat (lipid) and platelet storage and/or one or both eyes being abnormally small (microphthalmos). There may also be delayed physical and mental development. Chediak-Higashi Syndrome is characterized by abnormalities of the white blood cells (leukocytic disease), predisposition to infections and a high risk of lymphatic (lymphoreticular) malignancies.

Types of Ocular Albinism include Nettleship Falls Syndrome (X-linked), and Forsius-Eriksson syndrome (X-linked).

Symptoms of Albinism develop due to a lack of the enzyme tyrosinase. Melanin is a brown or black pigment that is usually present in the skin, hair and the iris of the eye. Tyrosinase is an enzyme that acts to convert tyrosine into melanin. Melanin is then stored in special pigment-carrying cells known as melanocytes. If tyrosinase is absent and/or does not function properly, melanin is not incorporated into the melanocytes nor maintained in these cells. This results in the absence of color in the skin, hair and eyes. People with Albinism generally have an even distribution of melanocytes but the sacs that typically contain the melanin (melanosomes) are empty.

Most of the Oculocutaneous forms of Albinism are inherited as an autosomal recessive trait. Partial Albinism or Albinoidism is inherited as an autosomal dominant trait. The Ocular types of Albinism may be inherited as an autosomal dominant, recessive or X-linked genetic traits. The defective gene thought to cause Forsius-Eriksson Syndrome or Type II Ocular Albinism has been located to the short arm of the X chromosome (position 21). The defective gene that is responsible for Type II Tyrosinase Positive Oculocutaneous Albinism has been located on the long arm of chromosome 15 (15q11-q13). The defective gene responsible for autosomal recessive Ocular Albinism has been mapped to chromosome 15 (15q11.2-q12).

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

X-linked recessive disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a 50 percent risk of transmitting the carrier condition to their daughters, and a 50 percent risk of transmitting the disease to their sons.

The occurrence of all forms of Albinism is approximately 1 in 10,000 people in the United States. Albinism is more common in some isolated communities, such as the Amish or Mennonite groups in the United States. Albinism affects males and females equally except the X-linked forms of this disorder that affect only males.

Symptoms of the following disorders can be similar to those of Albinism. Comparisons may be useful for a differential diagnosis:

Menkes Disease is a rare inherited genetic disturbance of copper metabolism. This disorder begins before birth and results in abnormally low levels of copper in many body tissues. Changes may occur in the hair, brain, bones, liver and arteries. Newborns are often born prematurely and symptoms may include an abnormally low body temperature (hypothermia), general weakness, poor appetite and a yellow appearance due to excess amount of bile in the blood (hyperbilirubinemia or jaundice). Most newborns with Menkes Disease appear normal and some may have characteristic pudgy cheeks. At the age of about 6 weeks, the fine hair of the newborn loses color (pigment). The hair eventually becomes kinky, tangled and sparse. Neurological symptoms usually occur around the age of 1 to 3 months. These symptoms may include generalized muscular rigidity, (hypertonia), irritability, feeding difficulties, convulsions and/or swelling in the brain caused by an accumulation of blood (subdural hematoma). Blot clots may also form within the blood vessels of the brain (cranial thrombosis) and the child may experience seizures. Developmental delay is often apparent. (For more information on this disorder, choose "Menkes" as your search term in the Rare Disease Database.)

There is no cure for the inherited metabolic defect that causes Albinism. People with Albinism require protection from sunlight, especially for those people with Oculocutaneous Albinism Syndromes. Sunglasses, protective clothing, and sun-protective lotions (containing para-aminobenzoic acid or PABA) are helpful. Visual aids may partially correct vision. Surgery to correct an eye that is either crossed or looking away (strabismus) may offer cosmetic results but no improvement in vision due to the abnormalities of the optic nerve. Treatment of other features of the various types of Albinism is symptomatic. In Chediak-Higashi Syndrome, it is reported that high doses of ascorbic acid may reduce some consequences of the lipid (fat-like substances) storage defects.

Genetic counseling will be of benefit for patients and their families.

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com.

Currently (2007) there are three clinical trials listed on www.clinicaltrials.gov that investigate aspects of albinism. Two of these studies deal with Hermansky-Pudlak syndrome. The third is focusing on individuals affected by Chediak-Higashi syndrome and related disorders.

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