Incidence and clinical features of hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) and spectrum of mevalonate kinase (MVK) mutations in German children

Rheumatol Int. 2012 Oct;32(10):3253-60. doi: 10.1007/s00296-011-2180-8. Epub 2011 Oct 30.


Autoinflammatory diseases (AIDs) are characterized by recurrent, self-limiting systemic inflammation. Disorders include hereditary recurrent fever (HRF) syndromes such as hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). To determine the incidence of HIDS and report clinical and genetic characteristics together with the underlying MVK genotypes in German children, a prospective active surveillance was conducted in Germany during a period of 3 years. Monthly inquiries were sent to 370 children's hospitals by the German Paediatric Surveillance Unit (Clinic-ESPED, n1) and to two laboratories (Laboratory-ESPED, n2) performing genetic analyses. Inclusion criteria were a MVK mutation-positive patient ≤16 years of age with more than three self-limiting episodes of fever >38.5°C associated with increased inflammation markers. Clinical, epidemiological, and genetic data were assessed via questionnaires. Eight out of 16 patients were identified in Clinic-ESPED (n1) and 15 of 16 in Laboratory-ESPED (n2). Clinical and laboratory surveys overlapped in 7 of 16 cases. Incidence of HIDS was estimated to be 0.39 (95% CI: 0.22, 0.64) per 10(6) person-years. HIDS symptoms generally started in infancy with recurrent fever episodes lasting 3-12 (median, 4.5) days and recurring every 1-12 weeks. Fever was accompanied by abdominal pain, vomiting, diarrhea, cervical lymphadenopathy, and sometimes by headache, skin and joint symptoms. The patients carried 11 different MVK mutations mostly in compound heterozygosity (75%, 12 out of 16). The most frequent mutation was p.Val377Ile (81%, 13 out of 16). In Germany, the incidence of HIDS is very low with 0.39 per 10(6) person-years.

MeSH terms

  • Adolescent
  • Age of Onset
  • Child
  • Child, Preschool
  • DNA Mutational Analysis
  • Female
  • Genetic Predisposition to Disease
  • Germany / epidemiology
  • Heterozygote
  • Humans
  • Incidence
  • Infant
  • Male
  • Mevalonate Kinase Deficiency / diagnosis
  • Mevalonate Kinase Deficiency / enzymology
  • Mevalonate Kinase Deficiency / epidemiology
  • Mevalonate Kinase Deficiency / genetics*
  • Mevalonate Kinase Deficiency / therapy
  • Mutation*
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Prognosis
  • Prospective Studies
  • Surveys and Questionnaires
  • Time Factors


  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase