Summary about Disease
Xeroderma pigmentosum complementation group A (XP-A) is a severe form of Xeroderma pigmentosum (XP), a rare autosomal recessive genetic disorder characterized by extreme sensitivity to ultraviolet (UV) radiation. Individuals with XP-A have a highly deficient DNA repair mechanism, specifically in nucleotide excision repair (NER), making them unable to efficiently repair DNA damage caused by UV light. This leads to a dramatically increased risk of skin cancers, neurological abnormalities, and a shortened lifespan.
Symptoms
Severe sunburn after minimal sun exposure (often the first sign, even with short exposures)
Excessive freckling at a young age (often before age 2)
Dry, scaly skin (xeroderma)
Changes in skin pigmentation (hypo- and hyperpigmentation)
Thinning skin with prominent blood vessels (telangiectasias)
Increased risk of skin cancers (basal cell carcinoma, squamous cell carcinoma, melanoma) at a young age
Eye problems: sensitivity to light (photophobia), corneal clouding, eyelid tumors
Neurological abnormalities (in some XP-A patients): developmental delays, progressive intellectual deterioration, spasticity, deafness, seizures
Causes
XP-A is caused by mutations in the XPA gene. This gene provides instructions for making a protein crucial for nucleotide excision repair (NER). NER is a vital DNA repair pathway that removes UV-induced DNA damage. Mutations in *XPA* lead to a non-functional or deficient XPA protein, resulting in impaired NER and the accumulation of DNA damage after UV exposure. This inherited genetic disorder is autosomal recessive, meaning that both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
There is no cure for XP-A. Treatment focuses on managing symptoms and preventing complications.
Sunscreen: High SPF, broad-spectrum sunscreen is critical and must be applied frequently and liberally.
Topical Medications: Creams and ointments to manage dry skin and precancerous lesions (e.g., fluorouracil, imiquimod).
Surgery: Excision of skin cancers.
Chemotherapy/Radiation Therapy: May be used for advanced skin cancers.
Eye Drops: To manage dry eyes and other eye problems.
Vitamin D supplementation: May be required due to extreme sun avoidance.
Retinoids: May be used topically or orally to manage precancerous or cancerous skin lesions.
Is Communicable
No, XP-A is not communicable. It is a genetic disorder passed down from parents to their children.
Precautions
Strict Sun Avoidance: The most crucial precaution. Avoid direct sunlight at all costs, especially between 10 am and 4 pm.
Protective Clothing: Wear long sleeves, pants, wide-brimmed hats, and UV-protective sunglasses when outdoors.
UV-Protective Film: Install UV-protective film on windows in homes and cars.
Regular Skin Exams: Frequent self-exams and professional skin exams by a dermatologist are essential for early detection of skin cancers.
Eye Protection: Wear UV-protective sunglasses and seek regular eye exams.
Genetic Counseling: For families with a history of XP-A.
How long does an outbreak last?
XP-A is a chronic condition, not an acute outbreak. Individuals with XP-A experience ongoing sensitivity to UV radiation throughout their lives. Skin cancer and other complications develop over time due to cumulative UV damage.
How is it diagnosed?
Clinical Examination: Based on characteristic symptoms like extreme sun sensitivity, freckling, and skin changes.
Family History: Review of family history to assess risk.
Skin Biopsy: A small skin sample is examined under a microscope to look for signs of UV damage and cancer.
Cellular Assays: Fibroblasts (skin cells) are cultured and tested for their ability to repair UV-induced DNA damage. Measuring the repair rate confirms the diagnosis.
Genetic Testing: Analysis of the XPA gene to identify disease-causing mutations.
Timeline of Symptoms
Infancy/Early Childhood:
Severe sunburn after minimal sun exposure (often the initial indicator)
Excessive freckling develops rapidly
Childhood/Adolescence:
Dry, scaly skin becomes more prominent
Changes in skin pigmentation appear
Eye problems (photophobia, corneal clouding) may start
Skin cancers may begin to develop (earlier than in the general population)
Neurological symptoms (in some XP-A patients) may become apparent
Adulthood:
Increased risk of multiple skin cancers
Continued skin and eye problems
Progression of neurological abnormalities (if present)
Important Considerations
Multidisciplinary Care: Management of XP-A requires a team of specialists, including dermatologists, ophthalmologists, neurologists, and geneticists.
Psychological Support: The chronic nature of the disease and the need for extreme lifestyle changes can have a significant emotional impact on individuals and families. Counseling and support groups can be helpful.
Early Diagnosis: Early diagnosis and strict sun avoidance are crucial to minimize the risk of complications and improve the quality of life.
Research: Ongoing research is aimed at developing new therapies for XP-A, including gene therapy and other approaches to enhance DNA repair.
Adherence: Strict adherence to sun protection guidelines is crucial to minimise the risks of associated complications.