title: Observational Study of a French and Belgian Multicenter Cohort of 23 Patients Diagnosed in Adulthood With Mevalonate Kinase Deficiency.
abstract: The aim of this study was to describe the clinical and biological features of Mevalonate kinase deficiency (MKD) in patients diagnosed in adulthood. This is a French and Belgian observational retrospective study from 2000 to 2014. To constitute the cohort, we cross-check the genetic and biochemical databases. The clinical, enzymatic, and genetic data were gathered from medical records. Twenty-three patients were analyzed. The mean age at diagnosis was 40 years, with a mean age at onset of symptoms of 3 years. All symptomatic patients had fever. Febrile attacks were mostly associated with arthralgia (90.9%); lymphadenopathy, abdominal pain, and skin lesions (86.4%); pharyngitis (63.6%); cough (59.1%); diarrhea, and hepatosplenomegaly (50.0%). Seven patients had psychiatric symptoms (31.8%). One patient developed recurrent seizures. Three patients experienced renal involvement (13.6%). Two patients had angiomyolipoma (9.1%). All but one tested patients had elevated serum immunoglobulin (Ig) D level. Twenty-one patients had genetic diagnosis; most of them were compound heterozygote (76.2%). p.Val377Ile was the most prevalent mutation. Structural articular damages and systemic AA amyloidosis were the 2 most serious complications. More than 65% of patients displayed decrease in severity and frequency of attacks with increasing age, but only 35% achieved remission. MKD diagnosed in adulthood shared clinical and genetic features with classical pediatric disease. An elevated IgD concentration is a good marker for MKD in adults. Despite a decrease of severity and frequency of attacks with age, only one-third of patients achieved spontaneous remission.
authors.affiliation: From the Internal Medicine Department, Edouard Herriot Hospital, Lyon (C-AD, BC, JN, M-HG-M, AH); Internal Medicine Department, Côte de Nacre Hospital, Caen (AA, BB, SD); Medicine and Rheumatology Department, Saint-Louis Hospital, La Rochelle (BG); Inborn Errors of Metabolism Laboratory, Civil Hospital of Lyon, Bron (CA-B); Internal Medicine Department, Claude Huriez Hospital, Lille (EH, P-YH); Polyvalent Medicine Department, Cornouaille Hospital Center, Quimper (FL, PH); Autoinflammatory Diseases Medical Unit, Arnaud Villeuneuve Hospital, Montpellier (IT); Nephrology Department, Metropole Savoie Hospital Center, Chambéry (J-BP); Rheumatology Department, Louis Pasteur Hospital, Colmar (LM); Hematology Department, Arras Hospital Center, Arras, France (MB); Internal Medicine Department, Sart Tilman, Liège, Belgique (MM); Dermatology and Allergology Department, Saint-Eloi Hospital, Montpellier (NR-P); Internal Medicine Department, Saint-André Hospital, Bordeaux (PD); Nephrology Department, Lyon Sud Hospital Center, Pierre-Bénite (PT); Hematology Department, Princesse Grace Hospital Center, Monaco (PH); Internal Medicine Department, Saint-Vincent Hospital Center, Strasbourg (RC); Rheumatology Department, Charles Nicole Hospital, Rouen (TL); Department of Pediatrics, Necker-Enfants Malades Hospital, Paris (VB); Diabetology and Internal Medicine Department, Blois Hospital Center, Blois (VL); Internal Medicine Department, Bocage Central, Dijon (SA); Service de Biostatistique, Hospices civiles de Lyon, Université de Lyon 1, Villeurbanne; CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, Villeurbanne (DM-B); and Department of Biochemical Genetics, Hospital and Institut Cochin, Paris (LC), France.
authors.forename: Cécile-Audrey
authors.initials: CA
authors.lastname: Durel
authors.forename: Achille
authors.initials: A
authors.lastname: Aouba
authors.forename: Boris
authors.initials: B
authors.lastname: Bienvenu
authors.forename: Samuel
authors.initials: S
authors.lastname: Deshayes
authors.forename: Brigitte
authors.initials: B
authors.lastname: Coppéré
authors.forename: Bruno
authors.initials: B
authors.lastname: Gombert
authors.forename: Cécile
authors.initials: C
authors.lastname: Acquaviva-Bourdain
authors.forename: Eric
authors.initials: E
authors.lastname: Hachulla
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lecomte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Touitou
authors.forename: Jacques
authors.initials: J
authors.lastname: Ninet
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Philit
authors.forename: Laurent
authors.initials: L
authors.lastname: Messer
authors.forename: Marc
authors.initials: M
authors.lastname: Brouillard
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Girard-Madoux
authors.forename: Michel
authors.initials: M
authors.lastname: Moutschen
authors.forename: Nadia
authors.initials: N
authors.lastname: Raison-Peyron
authors.forename: Pascal
authors.initials: P
authors.lastname: Hutin
authors.forename: Pierre
authors.initials: P
authors.lastname: Duffau
authors.forename: Pierre
authors.initials: P
authors.lastname: Trolliet
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Hatron
authors.forename: Philippe
authors.initials: P
authors.lastname: Heudier
authors.forename: Ramiro
authors.initials: R
authors.lastname: Cevallos
authors.forename: Thierry
authors.initials: T
authors.lastname: Lequerré
authors.forename: Valentine
authors.initials: V
authors.lastname: Brousse
authors.forename: Vincent
authors.initials: V
authors.lastname: Lesire
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.forename: Delphine
authors.initials: D
authors.lastname: Maucort-Boulch
authors.forename: Laurence
authors.initials: L
authors.lastname: Cuisset
authors.forename: Arnaud
authors.initials: A
authors.lastname: Hot
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001530:Belgium / Q000453:epidemiology; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology*; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult