[2] Loss of POLA1 expression resulted in reduced levels of RNA:DNA hybrids in the cytosol and unexpectedly triggered aberrant immune responses (e.g. type I interferon production) which in part can account for the symptoms associated with XLPDR.

[2] Another trigger of the immunodeficiency phenotype is a functional deficiency of Natural killer (NK) cells, which are major players in innate antiviral immune system.

However, skin pathologies, recurrent lung infection, high titer of interferon type I in the blood, and impaired direct cytotoxicity of NK cells are the most common symptoms.

In females, the disease is characterized by skin rashes, linear hyperpigmentation following the Blaschko's lines, morphologically similar to stage 3 pigment incontinence.

Recently, a number of reports suggest encouraging results with the use of JAK inhibitors baricitinib and ruxolitinib in several distinct type I interferonopathies.

[5] Other options that may be worth considering in the future are interferon receptor neutralizing antibodies, which are being actively pursued in the treatment of lupus where they show particular promise.

A path for definitive treatment for XLPDR is at present unclear, but it is tempting to speculate whether the immunologic disturbance is predominantly driven by the hematopoietic compartment.