OBSOLETE: Xeroderma pigmentosum complementation group A

Xeroderma pigmentosum complementation group A (XP-A) is a severe form of xeroderma pigmentosum, a rare autosomal recessive disorder caused by mutations in the XPA gene, which plays a critical role in the nucleotide excision repair (NER) pathway. This Orphanet entry (276249) is marked as OBSOLETE, meaning it has been retired and its clinical content has been merged into the broader xeroderma pigmentosum classification within Orphanet's nosology. Patients previously classified under this entry are now categorized under the general xeroderma pigmentosum entries. XP-A is characterized by extreme sensitivity to ultraviolet (UV) radiation, leading to severe sunburn reactions, freckling and pigmentary changes in sun-exposed skin beginning in early childhood, and a dramatically elevated risk of skin cancers including basal cell carcinoma, squamous cell carcinoma, and melanoma. The eyes are also significantly affected, with photophobia, keratitis, and increased risk of ocular surface neoplasms. XP-A is notably one of the most severe complementation groups and is frequently associated with progressive neurological degeneration, including microcephaly, sensorineural hearing loss, cognitive decline, peripheral neuropathy, and cerebellar ataxia. These neurological features distinguish XP-A from milder complementation groups. There is no cure for XP-A. Management is centered on rigorous UV protection, including avoidance of sunlight, use of protective clothing, UV-filtering eyewear, and regular dermatological surveillance for early detection and treatment of skin cancers. Neurological complications are managed supportively. Research into gene therapy and pharmacological approaches is ongoing but no disease-modifying treatments are currently approved.

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