Xeroderma Pigmentosum

XERODERMA PIGMENTOSUM WHAT IS IT? a rare, inherited disorder characterized by extreme sensitivity to ultraviolet (UV) rays from sunlight Usually appears in infancy/early childhood most often detected at 1-2 years of age most persons with XP die of skin cancer less than 40% of patients survive beyond age 20 years early in adulthood AFFECTS 1 IN 40,000 IN JAPAN 1 IN 250,000 IN THE USA AND EUROPE SYMPTOMS blistering after a bit of sun exposure patches of crusted, scaling, and discolored skin discomfort sunburn that does not heal in bright light oozing raw skin surface development of skin cancer BIOCHEMISTRY When exposed to UV rays, the DNA in the epidermal cells get damaged. Ha dimer is formed from the covalent bonding of two adjacent thymines the dimer destroys the structure of the DNA alpha helix Normally, these lesions would be repaired by the body through a process called nucleotide excision repair (NER). BUT! A person with Xeroderma Pigmentosum will have a defect on either one of the genes encoding for the enzymes that are part of the NER process. Genes that commonly have the defect: XPA (Xeroderma Pigmentosum, complementation group A) XPC (Xeroderma Pigmentosum, complementation group C) These genes encode for the enzymes that are in charge of verifying the damage in the DNA, resulting to the following: production of the protein needed for the repair stabilization of the DNA during the NER process IN SUMMARY gene mutation > enzyme malfunction > ineffective NER > persistence of lesions > physical defects TREATMENT SPF intake of oral retinoids DNA repair enzyme delivery sun avoidance use of sunscreen gene therapy COMPLICATIONS develop multiple cutaneous neoplasms • new and abnormal growith in the skin, at a young age • can either be benign or malignant USUAL CAUSES OF DEATH RIP squamous cell carcinoma metastatic malignant melanoma • liver, lungs, bones, & brain are most affected by metastases