Mevalonate kinase deficiency (MKD) is an autosomal recessive[2] metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids.

MKD is due to a pathogenic variants in the gene that encodes mevalonate kinase which results in a reduced or deficient activity of this enzyme.

MKD is a periodic fever syndrome originally described in 1984 by the internist Jos van der Meer,[4] then at Leiden University Medical Centre.

[citation needed] MKD is characterized by attacks of fever, arthralgia, skin lesions including cyclical mouth ulcers, and diarrhea.

[7][8] Indeed, similar fever attacks have been described in patients with mevalonic aciduria—an inborn error of metabolism now seen as a severe form of MKD.

[5] There is an increased secretion of the fever promoting cytokine interleukin 1 beta (IL-1β) in MKD, most likely mediated by defective protein prenylation.

In a human monocytic MKD model it was found that the deficiency of GGPP leads to overproduction of IL-1β and defective prenylation of RhoA.

As a result, mitochondrial DNA starts accumulating in the cytosol, binding and activating NLRP3, which is responsible for the production of IL-1β.

[9] It is known that monocytes and macrophages in affected individuals also produce higher levels of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) other than IL-Iβ[9] During febrile (fever) attacks, C-reactive protein (CRP) also increases.

[10] Defects in protein prenylation appear to drive the inflammatory phenotype by leading to activation of the pyrin and NLRP3 inflammasome through loss of RhoA and Rac1 membrane localization.