Mevalonate Kinase Deficiency

Abstract

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.