Molecular analysis of the mevalonate kinase gene in a cohort of patients with the hyper-igd and periodic fever syndrome: its application as a diagnostic tool

Ann Intern Med. 2001 Sep 4;135(5):338-43. doi: 10.7326/0003-4819-135-5-200109040-00010.


Background: The hyper-IgD and periodic fever syndrome (HIDS) is characterized by recurrent attacks of fever, abdominal distress, and arthralgia and is caused by mevalonate kinase mutations.

Objective: To ascertain the role of mevalonate kinase and the usefulness of molecular diagnosis in HIDS.

Design: Cross-sectional study.

Setting: The international Nijmegen HIDS registry.

Patients: 54 patients from 41 families who met the clinical criteria for HIDS.

Measurements: Clinical symptoms and signs, immunoglobulin concentration, leukocyte count, erythrocyte sedimentation rate, mutation analysis, and mevalonate kinase enzyme activity assay.

Results: There were two groups of patients: 41 patients with mevalonate kinase mutations (classic-type HIDS) and 13 patients without mutations (variant-type HIDS). Patients with classic-type HIDS had a lower mevalonate kinase enzyme activity, a higher IgD level, and more additional symptoms with attacks. The IgD level did not correlate with disease severity, mevalonate kinase enzyme activity, or genotype.

Conclusion: Genetic heterogeneity exists among patients with a clinical diagnosis of HIDS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Cross-Sectional Studies
  • Familial Mediterranean Fever / diagnosis
  • Familial Mediterranean Fever / enzymology*
  • Familial Mediterranean Fever / genetics*
  • Familial Mediterranean Fever / immunology
  • Female
  • Humans
  • Hypergammaglobulinemia / enzymology*
  • Hypergammaglobulinemia / genetics*
  • Hypergammaglobulinemia / immunology
  • Immunoglobulin D* / blood
  • Immunoglobulins / blood
  • Male
  • Mutation, Missense
  • Phenotype
  • Phosphotransferases (Alcohol Group Acceptor) / genetics*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Sequence Deletion


  • Immunoglobulin D
  • Immunoglobulins
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase