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

Background: The hyper-IgD and periodic fever syndrome (HIDS) is characteriz ed 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 HI DS. Measurements: Clinical symptoms and signs, immunoglobulin concentration, le ukocyte count, erythrocyte sedimentation rate, mutation analysis, and meval onate kinase enzyme activity assay. Results: There were two groups of patients: 41 patients with mevalonate kin ase mutations (classic-type HIDS) and 13 patients without mutations (varian t-type HIDS). Patients with classic-type HIDS had a lower mevalonate kinase enzyme activity, a higher IgD level, and more additional symptoms with att acks. The IgD level did not correlate with disease severity, mevalonate kin ase enzyme activity, or genotype. Conclusion: Genetic heterogeneity exists among patients with a clinical dia gnosis of HIDS.