Hyperimmunoglobulin D Syndrome (HIDS) / Mevalonate Kinase Deficiency (MKD) (Juvenile)

Mevalonate kinase deficiency (MKD), formerly called hyperimmunoglobulin-D syndrome (HIDS), is a rare, genetic disease that causes repeated episodes of fever and other symptoms. It is caused by an abnormal gene for the protein mevalonate kinase (MVK) and is mostly found in children of European ancestry. MKD affects both boys and girls, and symptoms can appear in infancy.

What Are the Signs/Symptoms?

Repeated episodes of fever are the main symptom of MKD. They may last for 3 to 7 days and happen every 2–12 weeks. Episodes begin suddenly, usually with chills. Children often have headaches, abdominal pain, appetite loss, flu-like symptoms, nausea, vomiting and diarrhea. Skin rashes all over the body, including painful mouth sores, can happen. Children may have joint pain and swelling, or muscle aches. You can easily see or feel swollen lymph nodes. Diagnosis of MKD must be made by a clinician with skill in this type of disease. During an episode, blood tests may show high levels of inflammation. Many children with MKD/HIDS may have high levels of proteins called immunoglobulins (especially –D and A). During episodes, urine tests will show high levels of mevalonic acid. A genetic test showing an abnormal MVK gene will confirm the diagnosis.

What are Common Treatments?

There is no cure for MKD, but treatments may help control inflammation and symptoms during episodes. Children may take nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin) or naproxen (Aleve, Naprosyn), or corticosteroids (such as prednisone) during an episode. Medications that block tumor necrosis factor (TNF) or interleukin-1 (IL-1) have been found to work to reduce the frequency of attacks. Anakinra (Kineret) may be used “on-demand” when an episode starts. Canakinumab (Ilaris) and etanercept (Enbrel) may be used regularly to prevent attacks in patients with more severe diseases.

Living with MKD

MKD episodes usually become milder and less frequent as children grow up. Yet, children may miss many days of school due to frequent episodes. It is important to tell other children and classmates that symptoms related to MKD are not contagious. Rarely, patients may get a problem called amyloidosis, which happens when there is too much inflammation. This is not common in the United States and usually doesn’t happen when the disease is treated appropriately. Regular medical check-ups to monitor for amyloidosis and other problems are important.

Updated March 2025 by Miriah Gillispie-Taylor, MD, and reviewed by the American College of Rheumatology Committee on Communications and Marketing.

This information is provided for general education only. Individuals should consult a qualified health care provider for professional medical advice, diagnosis and treatment of a medical or health condition.