Xeroderma pigmentosum

Xeroderma pigmentosa, 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. This disorder leads to multiple basaliomas and other skin malignancies at a young age. In severe cases, it is necessary to avoid sunlight completely. The two most common causes of death for XP victims are metastatic malignant melanoma and squamous cell carcinoma. XP is about six times more common in Japanese people than in other groups.

Cause
The most common defect in xeroderma pigmentosum is an autosomal recessive genetic defect whereby nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER.

Unrepaired damage can lead to mutations, altering the information of the DNA in individual cells.

If mutations affect important genes, like tumour suppressor genes (e.g. p53) or proto oncogenes then this disorder may lead to cancer.

Patients exhibit elevated risk of developing cancer, such as basal cell carcinoma.

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 CPD's (cyclobutane-pyrimidine-dimers) and 6-4PP's (pyrimidine-6-4-pyrimidone photoproducts).

The normal repair process entails nucleotide excision.

The damage is excised by endonucleases, then the gap is filled by a DNA polymerase and "sealed" by a ligase.

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

Symptoms
Some of the most common symptoms of XP include:


 * An unusually severe sunburn after a short sun exposure. The sunburn may last for several weeks. The sunburn usually occurs during a child's first sun exposure.
 * Development of many freckles at an early age.
 * Irregular dark spots on the skin.
 * Thin skin.
 * Excessive dryness of skin.
 * 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.
 * Premature aging of skin, lips, eyes, mouth and tongue.
 * Crusting skin
 * Spidery blood vessels
 * Scaly skin
 * Oozing raw skin surface
 * Limited growth of hair on chest and legs.

Treatment
The most important part of managing the condition is reducing exposure to the sun. The number of keratoses can be reduced with Isotretinoin (though there are significant side-effects.) Existing keratoses can be treated using cryotherapy or fluorouracil.

In Popular Culture
Christopher Snow, the protagonist and narrator of Dean Koontz' Moonlight Bay Trilogy of novels (Fear Nothing, Seize The Night and the to-be-completed Ride The Storm), has severe enough XP that he must avoid sunlight and as much artificial light as possible at all costs, living his life at night and then only by dim bulbs and candlelight, though always maintaining a positive and envigorated attitude about life, even authoring a best-selling autobiographical book on living with XP.

In Jodi Picoult's novel 'Second Glance' nine year old character Ethan Wakeman suffers from XP so severe he can only leave the house after sunset.

Alejandro Amenábar's Award-winning film, The Others, centers around a woman (Nicole Kidman) whose children suffer from XP and must be kept indoors, behind closed curtains, at all times.

'A Cool Moonlight', written by Angela Johnson, also deals with eight year old Lila who suffers from XP. Her XP is so bad that she is sometimes burned by streetlamps or certain lightbulbs.

Yui stars in a romantic Japanese movie Taiyō no Uta, where she plays the lead character, a street musician named Kaoru Amane, who is diagnosed with Xeroderma Pigmentosum and only performs at night because of this disease. Even with this diagnosis, she chases her dreams of becoming a singer and meets Kōji Fujishiro (Takashi Tsukamoto), who also has a passion for music and whom Kaoru eventually falls in love with. This story was also the basis for a Japanese TV drama series, also called "Taiyō no Uta", starring Erika Sawajiri and Takayuki Yamada in the roles of Kaoru and Kōji.