title: Homozygosity for the V377I mutation in mevalonate kinase causes distinct clinical phenotypes in two sibs with hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS).
abstract: 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.
authors.affiliation: Service de Rhumatologie , Hôpitaux Civils de Colmar , Colmar , France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Messer
authors.affiliation: Faculté de Médecine, Laboratoire d'ImmunoRhumatologie Moléculaire , INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg , Strasbourg , France.
authors.forename: Ghada
authors.initials: G
authors.lastname: Alsaleh
authors.affiliation: Faculté de Médecine, Laboratoire d'ImmunoRhumatologie Moléculaire , INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg , Strasbourg , France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Georgel
authors.affiliation: Faculté de Médecine, Laboratoire d'ImmunoRhumatologie Moléculaire , INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg , Strasbourg , France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Carapito
authors.affiliation: Laboratory Genetic Metabolic Diseases (F0-222), Departments of Clinical Chemistry and Pediatrics , Academic Medical Center, University of Amsterdam , Amsterdam , The Netherlands.
authors.forename: Hans R
authors.initials: HR
authors.lastname: Waterham
authors.affiliation: Laboratoire de Biochimie et de Biologie Moléculaire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)/CNRS UMR 7104/INSERM U 964/Université de Strasbourg, Illkirch, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Dali-Youcef
authors.affiliation: Faculté de Médecine, Laboratoire d'ImmunoRhumatologie Moléculaire , INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg , Strasbourg , France.
authors.forename: Siamak
authors.initials: S
authors.lastname: Bahram
authors.affiliation: Faculté de Médecine, Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx Transplantex, Centre de Recherche d'Immunologie et d'Hématologie, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France; Service de Rhumatologie, Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
keywords: Disease Activity; Gene Polymorphism; Inflammation