Rare diseases Xagena

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Disseminated superficial actinic porokeratosis, a rare inherited skin condition

Disseminated superficial actinic porokeratosis ( DSAP ) is a disease described in 1966 by Chernosky, and represents the most common form of porokeratosis, a group of diseases characterized by epidermal cornification with epidermal cell hyperproliferation and premature apoptosis of keratinocytes.
Triggers include ultraviolet light exposure and immunosuppression.
Multiple small ( 0.5-1 cm ) round and brownish lesions surrounded by a hyperkeratotic rim develop on sun-exposed areas of the skin particularly on the lower legs and forearms.
Lesions usually appear in summer and improve or disappear during winter. The disease usually starts during the third or fourth decades of life, and rarely affects children.
While it is usually benign, squamous cell carcinoma or Bowen’s disease may occasionally develop within the lesions.

Histopathological examination of the skin sampled from the edge of the peripheral rim characteristically shows an angulated cornoid lamella and a parakeratotic column overlying an area of epidermis with an absent or reduced granular layer.
Differential diagnosis includes neoplastic or hyperplastic squamous skin lesions.

Cryotherapy, topical reagents ( retinoids, Imiquimod, 5-Fluorouracil, keratolytic ), electrodessication, laser ablation or photodynamic therapy are used to destroy the abnormal keratinocyte clones.

The mode of inheritance is dominant however many sporadic cases of porokeratosis have been described. Mutations in the MeValonate Kinase ( MVK ) gene were found in DSAP patients.
The MVK enzyme is involved in the biosynthesis of cholesterol and isoprenoid. It is also thought to play a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation.

All genetically confirmed patients are of Chinese origin. Fourteen different mutations have been found, among which, 10 accounted for one third of the familial cases. Mutations in this gene were initially demonstrated as responsible for recessive complete ( mevalonic aciduria ) and incomplete ( hyperIgD syndrome ) mevalonate kinase deficiency. ( Xagena )

Touitou I et al, Orphanet Journal of Rare Diseases 2013, 8:162