Can Genetics Help Diagnose the Hyper-IgD and Periodic Fever Syndrome? FREE

Periodic fever is an uncommon condition defined by recurring bouts of fever in people who seem healthy except during their fever attacks. The condition is hard to diagnose because there are several types of periodic fever as well as multiple causes of recurring fevers. In 1984, researchers identified a type of periodic fever that they called the hyper-IgD and periodic fever syndrome (HIDS). People with HIDS have persistently high levels of an antibody known as immunoglobulin D (IgD). They have recurring bouts of high fever with swollen lymph nodes, abdominal distress (vomiting, diarrhea, and pain), and joint pain. Symptoms last for several days and recur every few weeks. Researchers think that the underlying cause of HIDS is a mutation of a specific gene (the mevalonate kinase gene). This mutation can be identified with special molecular genetic tests. Whether the tests can be used to diagnose HIDS is unclear, however.

To find out whether molecular genetic tests for mutations in the mevalonate kinase gene are useful for diagnosing HIDS.

The researchers studied 54 patients with HIDS who were identified from a special registry in the Netherlands. All had repeated bouts of fever, with clinical findings such as swollen lymph glands, joint pain, skin rashes, or abdominal symptoms. The patients also had persistently high levels of IgD.

The researchers analyzed cell samples and DNA obtained from patients' blood. They looked for mutations in the mevalonate kinase gene.

Forty-one of the 54 patients with clinically diagnosed HIDS had mutations in their mevalonate kinase gene. The patients with the gene mutations had much higher IgD levels and more symptoms with their fever bouts than did the patients without mutations. They also more often had siblings with HIDS.

Because the study did not include patients with other types of recurring or periodic fevers, it could not determine the usefulness of molecular genetic testing in distinguishing HIDS from other fever syndromes.

Mutations in the mevalonate kinase gene appear to be common among people with clinically diagnosed HIDS. However, because molecular genetic tests for these mutations are not always positive, they cannot be used to rule out the diagnosis of HIDS.