Mevalonate Kinase Deficiency

  • Joost Frenkel
  • Anna SimonEmail author


Mevalonate kinase deficiency (MKD) is a rare autoinflammatory disease caused by loss of function mutations in both alleles of MVK, the gene encoding the enzyme mevalonate kinase. Deficiency of this enzyme results in impaired isoprenoid biosynthesis. The inflammatory attacks in MKD are characterized by fever, lymphadenopathy, gastrointestinal symptoms, aphthous ulcers, rash, arthralgias and/or arthritis. Severely affected patients may in addition have neurological involvement, cataract, uveitis, and failure to thrive, often dying in early childhood. This severe end of the phenotypic spectrum is called mevalonic aciduria (MA) as opposed to the milder phenotype also known as hyperimmunoglobulinemia D periodic fever syndrome (HIDS). In this chapter, we detail clinical phenotype and pathophysiological background as well as treatment options.


Mevalonate kinase deficiency Mevalonic aciduria Periodic fever Hyperimmunoglobulinemia D syndrome Autoinflammatory Isoprenoid metabolism 



Cryopyrin-associated periodic syndrome


C-reactive protein


Disseminated superficial actinic porokeratosis


European Medicines Agency


Food and Drug Administration (FDA)


Farnesyl diphosphate synthase


Familial Mediterranean fever


Gas chromatography-mass spectrometry


Hyperimmunoglobulinemia D syndrome


Hydroxymethylglutaryl-coenzyme A


Immunoglobulin D




Mevalonic aciduria


Mevalonate kinase


Mevalonate kinase deficiency


Mevalonate decarboxylase


Mevalonate kinase gene


Non-steroidal anti-inflammatory drugs


Peripheral blood mononuclear cells


Periodic fever, aphthous stomatitis, pharyngitis, adenitis


Phosphomevalonate kinase


Serum amyloid A


Tumor necrosis factor


TNF receptor-associated periodic syndrome


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Wilhelmina’s Children’s Hospital, University Medical CenterUtrechtThe Netherlands
  2. 2.Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and AutoinflammationRadboud University Medical CenterNijmegenThe Netherlands

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