RT Journal Article SR Electronic T1 Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) JF RMD Open JO RMD Open FD EULAR SP e000196 DO 10.1136/rmdopen-2015-000196 VO 2 IS 1 A1 Laurent Messer A1 Ghada Alsaleh A1 Philippe Georgel A1 Raphael Carapito A1 Hans R Waterham A1 Nassim Dali-Youcef A1 Siamak Bahram A1 Jean Sibilia YR 2016 UL http://rmdopen.bmj.com/content/2/1/e000196.abstract AB Objective Mevalonate kinase (MVK) deficiency is a rare autosomal recessive auto-inflammatory disorder characterised by recurring episodes of fever associated with multiple non-specific inflammatory symptoms and caused by mutations in the MVK gene. The phenotypic spectrum is wide and depends mostly on the nature of the mutations. Hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) is a relatively mild presentation and predominantly associated with a c.1129G>A (p.V377I) mutation in the MVK gene. We report cases of two sisters homozygous for this mutation but exhibiting distinct (symptomatic vs asymptomatic) phenotypes.Methods Patient history was obtained; physical and clinical examination and laboratory tests were performed; lipopolysaccharide (LPS) response of peripheral blood mononuclear cells was quantified.Results Low MVK enzymatic activity is not necessarily associated with inflammatory symptoms. Increased inflammatory cytokine secretion in response to LPS is associated with symptomatic MVK deficiency.Conclusions Individuals who are homozygous for the common p.V377I mutation in the MVK gene may not display the characteristic inflammatory episodes diagnostic of MKD and thus may be lost for correct and timely diagnosis.