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 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.