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Mevalonate Kinase Deficiency

  • Joost Frenkel
  • Anna SimonEmail author
Chapter

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.

Keywords

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

Abbreviations

CAPS

Cryopyrin-associated periodic syndrome

CRP

C-reactive protein

DSAP

Disseminated superficial actinic porokeratosis

EMA

European Medicines Agency

FDA

Food and Drug Administration (FDA)

FDPS

Farnesyl diphosphate synthase

FMF

Familial Mediterranean fever

GC-MS

Gas chromatography-mass spectrometry

HIDS

Hyperimmunoglobulinemia D syndrome

HMG-CoA

Hydroxymethylglutaryl-coenzyme A

IgD

Immunoglobulin D

IL-1

Interleukin-1

MA

Mevalonic aciduria

MK

Mevalonate kinase

MKD

Mevalonate kinase deficiency

MVD

Mevalonate decarboxylase

MVK

Mevalonate kinase gene

NSAIDs

Non-steroidal anti-inflammatory drugs

PBMC

Peripheral blood mononuclear cells

PFAPA

Periodic fever, aphthous stomatitis, pharyngitis, adenitis

PMVK

Phosphomevalonate kinase

SAA

Serum amyloid A

TNF

Tumor necrosis factor

TRAPS

TNF receptor-associated periodic syndrome

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© 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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