Xeroderma pigmentosum

Xeroderma pigmentosum, or XP, is an autosomal recessive genetic disorder of DNA repair in which the ability to repair damage caused by ultraviolet (UV) light is deficient. In extreme cases all exposure to sunlight must be forbidden, no matter how small. Multiple basal cell carcinomas (basaliomas) and other skin malignancies frequently occur at a young age in those with XP. In fact, metastatic malignant melanoma and squamous cell carcinoma are the two most common causes of death in XP victims. XP involves both sexes and all races with an incidence of 1:250,000 and a gene frequency of 1:200. XP is roughly six times more common in Japanese people than in other groups.

The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of Nucleotide Excision Repair. If left unchecked, damage caused by UV light can cause mutations in individual cell's DNA. If tumor suppressor genes (e.g. p53) or proto oncogenes are affected, the result may be cancer. Patients with XP are at a high risk for developing skin cancers, such as basal cell carcinoma, for this reason.

Normally, damage to DNA in epidermal cells occurs during exposure to UV light. The absorption of the high energy light leads to the formation of pyrimidine dimers, namely CPDs (cyclobutane-pyrimidine-dimers) and 6-4PPs (pyrimidine-6-4-pyrimidone photoproducts). In a healthy, normal human being, the damage is first excised, "cut out" by endonucleases. DNA polymerase then repairs the missing sequence, and ligase "seals" the transaction. This process is known as nucleotide excision repair.

Types
There are 7 complementation groups, plus one variant form :

Symptoms
Some of the most common symptoms of XP include:


 * A severe sunburn when exposed to only small amounts of sunlight. Often occurring during a child's first exposure to sunlight.
 * Development of many freckles at an early age
 * Rough-surfaced growths (solar keratoses), and skin cancers
 * Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot, and clouded
 * Blistering or freckling on minimum sun exposure
 * Spidery blood vessels
 * Oozing raw skin surface
 * Limited growth of hair on chest and legs
 * Scaly skin
 * Irregular dark spots on the skin

Treatment
The most obvious, and often important part of treatment is avoiding exposure to sunlight. Keratoses can also be treated using cryotherapy or fluorouracil. There are a few places which cater to XPS, one of most notable being Camp Sundown in Craryville, New York.

Prognosis
Fewer than 40% of individuals with the disease survive beyond age 20 years. Some XP victims with less severe cases of the disease do manage to live well into their 40s.

In popular culture

 * Christopher Snow in Dean Koontz' Moonlight Bay Trilogy.
 * In the 2002 novel "Going Out" by Scarlett Thomas the character Luke has XP.
 * Children of the main character in Alejandro Amenábar's 2001 film, The Others.
 * In the Japanese movie Taiyou no Uta also known as Midnight Sun, the main character suffers from XP.
 * In the ITV series Ultraviolet, one of the humans is mistaken for a vampire because he avoids sunlight, when in fact he has XP.
 * In the independent film "Dark Side of the Sun" (1988) with Brad Pitt as the main character suffering from XP.
 * In the 2003 novel "Second Glance" by Jodi Picoult. Ethan Wakeman, the 9 year old nephew of Ross Wakeman (the main protagonist), has XP.
 * In the 2003 Angela Johnson novel, "A Cool Moonlight", it centers on a girl who has XP and can't ever be in the sun. The family has gone to drastic measures to help make her life easier, and to make her feel like a normal 8-year-old.