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

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Fast Facts

  • HIDS / MKD is a genetic disease caused by an abnormality in a gene that codes a protein called mevalonate kinase (MVK).
  • Symptoms typically start in infancy and include recurring episodes of fever, rash, abdominal pain, diarrhea, joint pain, mouth sores, and swelling of lymph glands, lasting 4 days and recurring on a monthly basis. 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.
  • HIDS / MKD tends to ease over time and often resolves by adulthood.

Mevalonate Kinase Deficiency (MKD), formerly known as Hyperimmunoglobulin D Syndrome, is a 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 and A), 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 number of certain molecules that participate in the control of the process of inflammation. Episodes can be triggered by events that stimulate the immune system such as infection, stress, trauma, surgery and especially by vaccinations. Episodes can also 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 MVK/HIDS. Blood tests during an episode usually show signs of inflammation. Most have elevated levels of immunoglobulins D and A. 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?

Because MKD/HIDS is a genetic disorder, it cannot be cured, but its symptoms can be controlled. During an episode, nonsteroidal anti-inflammatory drugs (like ibuprofen and naproxen) or steroids may help. Biologic treatments that block inflammatory proteins such as interleukin-1 or tumor-necrosis-factor may prevent or decrease the frequency of attacks in most patients. Anakinra (Kineret), one of the interleukin-1 blockers, may be 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 be used regularly to prevent attacks in patients with more severe disease. Researchers continue to search for more 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. 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 may rarely develop a complication of inflammation called amyloidosis. In children with chronic inflammatory disease, amyloid is a protein that can deposit in the major organs. 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. Fortunately, this complication is extremely rare in the United States, and may be prevented by appropriate therapy.

Updated December 2021 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.

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