Hyperimmunoglobulin D Syndrome (Juvenile)

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Fast Facts

  • Mevalonate Kinase Deficiency is a genetic disease caused by an abnormality in a gene that codes a protein called mevalonate kinase (MVK).
  • Major symptoms include recurrent fever from infancy with rash, abdominal pain, diarrhea, joint pain, mouth sores and swelling of lymph glands. Episodes are often triggered by vaccines.
  • New biologic treatments may ease the disease for the majority of patients. The long-term outcome is usually good.
  • There is no proven treatment, but Mevalonate Kinase Deficiency/ Hyperimmunoglobulin D Syndrome tends to ease over time and often resolves by adulthood.

Mevalonate Kinase Deficiency (MKD) was formerly known as Hyperimmunoglobulin D Syndrome and is a very rare disease. The disease is mostly found in Western Europe, especially in the Netherlands and France, but has been described in all ethnic groups. Boys and girls are affected equally. Symptoms usually start in early childhood, most commonly in the first year of life.

What is Mevalonate Kinase Deficiency/ Hyperimmunoglobulin D Syndrome?

Mevalonate kinase deficiency (MVK), formerly called hyperimmunoglobulin D Syndrome (HIDS) is a genetic syndrome that results in episodes of high fever with skin rash, swollen lymph nodes in the neck, mouth sores, abdominal pain, vomiting, diarrhea and joint pain with swelling. Most patients have high amounts of proteins called immunoglobulins (especially D), which normally are used by the immune system to fight infections. The most severe form of this disease starts at birth and is called mevalonic aciduria. These patients also have severe neurologic (nervous system) disease and poor growth.

Fevers are the main symptom, usually lasting 3-7 days, and may recur every 2-12 weeks. The episodes begin suddenly, often with shaking chills. Headache, abdominal pain, loss of appetite and flu-like symptoms are common. Most patients experience nausea, vomiting or diarrhea. Skin rashes on all parts of the body—Including the hands and feet and painful sores in the mouth – may occur. One of the most striking features is swelling of the lymph nodes in the neck or other parts of the body. Patients may develop joint and muscle pain as well as joint swelling in small and large joints. Childhood vaccines are a common trigger of episodes in these patients.

What causes it?

Mevalonate Kinase Deficiency/ Hyperimmunoglobulin D Syndrome (MKD/HIDS) is a genetic disease. The gene defect results in abnormalities in a protein called mevalonate kinase (MVK). MVK is a protein that facilitates a chemical reaction in the body (an enzyme) involved in the process of making cholesterol. Thus Mevalonate Kinase Deficiency may be considered a “metabolic” disease.

It is not known why the gene defect causes fever, but it appears that the gene defect causes a decrease in the amount of certain molecules that participate in the control of the process of inflammation. Episodes can be triggered by infection, stress, trauma, surgery and especially vaccinations or can occur without any obvious trigger.

MKD/HIDS is inherited in an autosomal recessive manner, meaning that the child receives two mutated genes, one from the mother and the other from the father. The parents are then called carriers, and may not be ill at all. Often, someone in the extended family has the disease. If one child has the disease and the parents are carriers, there is a 25 percent chance another child will get MKD/ HIDS.

How is Mevalonate Kinase Deficiency/ Hyperimmunoglobulin D Syndrome diagnosed?

It usually takes a physician expert in this disease to diagnose this disease. Blood tests during an episode usually show signs of inflammation. Most (but not all-especially younger children) have elevated levels of immunoglobulin D. During episodes, a urine test for organic acids will show high levels of mevalonic acid. The diagnosis will be confirmed by a genetic test finding the defect in the MVK gene.

How is Mevalonate Kinase Deficiency/ Hyperimmunoglobulin D Syndrome treated?

MKD/HIDS cannot be cured. During an episode, nonsteroidal anti-inflammatory drugs (like ibuprofen and naproxen) or steroids may help. Recently it has been shown that certain biologic treatments that work against proteins affecting the immune system may prevent or decrease the frequency of attacks in most patients, particularly medications which block proteins called interleukin-1 or tumor-necrosis factor. These proteins are important in the process of inflammation. Anakinra (Kineret), one of the interleukin-1 blockers, is often used “on-demand” at the start of an episode. Canakinumab (Ilaris), also an interleukin-1 blocker and etanercept (Enbrel), a tumor-necrosis factor blocker may prevent attacks in patients with a more severe disease. Researchers continue to search for effective treatments.

Living with Mevalonate Kinase Deficiency/ Hyperimmunoglobulin D Syndrome

MKD/HIDS is a lifelong disorder, but episodes usually get milder and less frequent over time, often resolving in adulthood. Children with the condition may miss many days of school due to episodes. It is important to stress that the fever of MKD/HIDS is not contagious.

Patients rarely may develop a complication of inflammation called amyloidosis. Amyloid is a protein that deposits in certain organs in children with chronic inflammatory disease. The most common organ involved is the kidney, but amyloid can deposit in the intestines, skin and heart. Eventually, amyloid causes a loss of function, especially of the kidneys.

Updated May 2015. Written by Philip Hashkes, MD, MSc, Shaare Zedek Medical Center and the Hebrew University, Jerusalem, 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.

© 2015 American College of Rheumatology