X-linked reticulate pigmentary disorder

X-linked reticulate pigmentary disorder, also called XLPDR, is a rare X-linked genetic condition in which males have multiple systemic symptoms and a reticulated, mottled brown pigmentation of the skin that shows dermal deposits of amyloid on biopsy, while females usually have only linear streaks of hyperpigmentation. It was characterized in 1981. A mutation of the POLA1 gene leads to loss of expression of the catalytic subunit of DNA polymerase alpha and is responsible for the disorder; the loss of POLA1 expression triggers aberrant immune responses such as type I interferon production, and a functional deficiency of natural killer cells adds to the immunodeficiency. Affected males develop generalized reticular hyperpigmentation in early childhood, and common features include recurrent respiratory infections, corneal changes, photophobia, lack of sweat glands, growth retardation, gastrointestinal and kidney problems. Most patients stabilize with age. Diagnosis rests on finding the single intronic POLA1 variant, and management is largely supportive, with antibiotics for lung infections and, in reports, JAK inhibitors for type I interferon driven disease.