Hyper-IgD syndrome

What causes hyper IgD syndrome?

Hyper IgD syndrome is caused by mutations in the gene _MVK _which __ encodes the enzyme mevalonate kinase. The mutations lead to a partial deficiency of the enzyme mevalonate kinase. This enzyme converts a substance called mevalonic acid into mevalonate-5-phosphate. This conversion is the second step in a pathway that makes cholesterol. The cholesterol is later converted into steroid hormones and bile acids. Steroid hormones are needed for normal development and reproduction, and bile acids are used to digest fats. The enzyme also helps to produce other substances that are necessary for certain cellular functions, such as cell growth, cell maturation (differentiation), formation of the cell's structural framework (the cytoskeleton), gene activity (expression), and protein production and modification. A role for this pathway in inflammation is still not completely understood, but it is known that the mevalonate pathway produces cholesterol, and also some compounds which are necessary for the proper interaction and function of these proteins.

Last updated on 05-01-20

Is hyper IgD syndrome inherited?

Hyper IgD syndrome is inherited in an autosomal recessive manner, which means both copies of the gene in each cell have mutations. The parents of a person with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Last updated on 05-01-20

What is hyper IgD syndrome?

Hyper IgD syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency. It is considered an auto-inflammatory disease, with recurrent episodic or chronic unexplained inflammation, characterized by periodic episodes of fever, and other symptoms such as joint pain, swollen lymph nodes, skin rash, headaches, and abdominal pain. Most episodes last several days and occur periodically throughout life. The frequency of episodes and their severity vary greatly from person to person. These attacks can occur spontaneously or be triggered by vaccinations, infections, and/or emotional or physical stress. Growth and development is usually not affected. Hyper IgD syndrome is caused by mutations in the MVK gene which provides instructions for making the mevalonate kinase enzyme. The mutations result in the partial deficiency of the enzyme. A more severe form of maevalonate kinase deficiency is known as mevalonic aciduria. It is inherited in an autosomal recessive manner. Treatment is with anakinra, and other medications, but not all patients show a complete response. In most cases, the frequency of the disease's episodes decreases over time.

Last updated on 05-01-20

What factors may precipitate attacks in individuals with hyper IgD syndrome?

Fever episodes in individuals with hyper IgD syndrome can be triggered by vaccinations, surgery, injury, or stress.

Last updated on 05-01-20

Are there any foods that are known to trigger attacks in individuals with hyper IgD syndrome?

A search of the resources available to us did not identify any reports of foods that have been found to cause attacks in individuals with hyper IgD syndrome. We encourage you to discuss any specific factors which appear to trigger attacks in your particular case with your health care provider(s).

Last updated on 05-01-20

What is the prognosis for individuals with hyper IgD syndrome?

Life expectancy is not shortened except for in rare cases where severe infections or kidney amyloidosis occur. Between fever attacks, patients are generally free of symptoms. Attacks do continue throughout the lifetime, although there may be a slight decrease following adolescence. A long-term follow-up study showed that the frequency of the attacks decreases over time, but about half of the patients more than 20 years of age still experience six or more attacks per year, with quite an impact on quality of life.

Last updated on 05-01-20

How might hyper IgD syndrome be treated?

The mainstay of the treatment of hyper IgD is anakinra, but not all patients show a complete response. Usually five to seven daily injections are sufficient to prevent an early relapse. Anakinra can also be used to prevent vaccine-induced attacks in patients that need immunizations.

In 2015, a group of experts from different countries proposed recommendations for the management of several anti-inflammatory diseases including hyper IgD syndrome. Recommendations include:

  • NSAIDs may provide symptom relief during inflammatory attacks
  • Short-term glucocorticoids, with or without NSAIDs, may be effective for alleviating inflammatory attacks
  • Short-term IL-1 blocking agents (anakinra or canakinumab) may be effective for ending inflammatory attacks and should be considered to limit or prevent steroid side effects or as a maintenance therapy
  • If one IL-1-blocking agent at an adequate dose is ineffective or not well tolerated, a switch to another IL-1-blocking agent or another biological agent (including TNF-α blockers (etanercept (Enbrel), rituximab, o infliximab) or IL-6 blockade (tocilizumab) should be considered.
  • If TNF-α blocker is ineffective or intolerable, a switch to another biological agent (including an IL-1- or IL-6-blocking agent) should be considered.

In selected cases with severe disease that does not improve, and poor quality of life, referral to a specialist center for consideration of allogeneic hematopoietic stem cell transplantation is recommended.

Consultations with the following specialists may be helpful: dermatologist, rheumatologist, and infectious disease specialist (to evaluate periodic fever).

Last updated on 05-01-20

Where To Start

Hyper IgD syndrome

The Doctor's Doctor provides information about hyper IgD syndrome. Click on the link to view this information.

Last updated on 04-27-20

Name: FMF & AID Global Association Schüracherstrasse 25a 8306 Brüttisellen
Phone: +41 76 415 4010 Email: info@fmfandaid.org Url: https://www.fmfandaid.org/
Name: Rare Autoinflammatory Conditions Community - UK RACC-UK United Kingdom Phone: 07377091552 Email: info@raccuk.com Url: https://www.raccuk.com/

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