title: Hyper-IgD and periodic fever syndrome: a new MVK mutation (p.R277G) associated with a severe phenotype.
abstract: Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM# 260920) is a rare recessively-inherited autoinflammatory condition caused by mutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Here we report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non-consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, whereas anakinra showed positive responses only at high doses. The p.R277G mutation here described is a novel missense MVK mutation, and it has been detected in this case with a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.
authors.affiliation: Pediatric Department, Hospital Dona Estefânia, CHLC, EPE, Lisbon, Portugal. Electronic address: joanaasantos@gmail.com.
authors.forename: Joana A
authors.initials: JA
authors.lastname: Santos
authors.affiliation: Immunology Department, Hospital Clínic-IDIBAPS, Barcelona, Spain. Electronic address: JIAROSTE@clinic.ub.es.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Aróstegui
authors.affiliation: Pediatric Infectious Diseases Unit, Hospital Dona Estefânia, CHLC, EPE, Lisbon, Portugal. Electronic address: joao.rochabrito@netcabo.pt.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Brito
authors.affiliation: Primary Immunodeficiency, Hospital Dona Estefânia, CHLC, EPE, Lisbon, Portugal. Electronic address: conceicaoneves59@gmail.com.
authors.forename: Conceição
authors.initials: C
authors.lastname: Neves
authors.affiliation: Pediatric Rheumatology, Hospital Dona Estefânia, CHLC, EPE, Lisbon, Portugal. Electronic address: marta.c.conde@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Conde
mesh_terms: D000210:Acute-Phase Reaction / Q000235:genetics; D002675:Child, Preschool; D005334:Fever / Q000188:drug therapy / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007072:Immunoglobulin D / Q000097:blood / Q000235:genetics*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D008297:Male; D054078:Mevalonate Kinase Deficiency / Q000097:blood / Q000235:genetics; D020125:Mutation, Missense; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics*
chemical_list: D007072:Immunoglobulin D; D053590:Interleukin 1 Receptor Antagonist Protein; D017853:Phosphotransferases (Alcohol Group Acceptor); C021796:mevalonate kinase
keywords: Anakinra; Hyperimmunoglobulinemia D and periodic fever syndrome; Mevalonate kinase; New mutation; Phenotype