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Mevalonate Kinase Deficiency (MKD) also known as Hyper IgD Syndrome (HIDS)
MKD (HIDS) is an inherited auto inflammatory disease that is most often caused by an inherited autosomal recessive gene mutation of the mevalonate kinase gene (MVK), from both parents. However, there are cases of single-mutation dominant HIDS. Also, there are some that are clinically diagnosed with HIDS, where the patient has all the symptoms and findings associated with this disease, but the genetic mutation(s) have not been found with the current genetic testing.

HIDS is caused by the inherited MVK gene mutation. Clinical symptoms of HIDS, and the finding of MVK mutation(s)and elevated inflammatory markers during flares of symptoms, such as high C-reactive protein and ESR are helpful in diagnosing a patient with this disease. HIDS is a lifelong disease in many cases, but some patients have greatly reduced,or infrequent symptoms as adults.

Continuously high IgD values (more than 100 IU per milliliter) on 2-IgD lab tests done one month apart can help doctors to consider the diagnosis of HIDS in many patients. But this test is not accurate in children under 2-3 years of age, plus 20% of HIDS patients never have elevated IgD, and elevated IgD is noted at times with other autoinflammatory diseases (but not as often as it is with HIDS) so doctors should not rely on the IgD testing alone for a diagnosis. Over 80% of HIDS patients also have high IgA levels along with high IgD levels. During an attack, leukocytosis, high levels of C-reactive protein (CRP) and serum amyloid A are noted. Mevalonate aciduria is also noted in many cases.

The MVK gene mutation is uncommon, but in The Netherlands, 1:350 people carry the recessive gene mutation. In general, both parents have to carry the recessive gene mutation to lead to the autosomal recessive inheritance of HIDS symptoms in a child. Most HIDS patients are Caucasian, live in western European countries and 60 percent are either Dutch or French. There are some cases of patients that present with HIDS symptoms that have only one MVK mutation found.

Symptoms of HIDS are noted by the first year of life in most patients. Bouts of HIDS symptoms or attacks usually begin with chills, then a quick rise in temperature that causes a fever for 3-7 days. HIDS patients may (but not always) have a diffuse erythematous maculpapular rash, urticaria, headaches, joint pain, large joint arthritis, enlarged cervical lymph nodes, vomiting and diarrhea during the flares. Some patients have petechiae or purpura, and even painful aphthous mouth or vaginal ulcers. As with all other autoinflammatory diseases, these conditions are not infectious, and are generally caused by having a genetic mutation that causes this disease. Even during flares of fever with the accompanying symptoms, these patients are not infectious if they are suffering from a HIDS flare.

The intensity of HIDS symptoms begins to taper off after a few days of the flare. The attacks can occur with great frequency, often every two to six weeks, and are often triggered by vaccinations, minor trauma, stress, surgery or unknown causes.

Hyper IgD Syndrome (HIDS) presents with longer episodes of flare-ups than CAPS, and a different rash. Once the attack is over, patients are free of symptoms, but it may take awhile for the joint pain and skin rash to fully disappear. Patients can have attacks off and on throughout their life, and patients can sometimes be free of symptoms for many months or even years in some cases. Generally, patients have the greatest frequency of HIDS attacks during childhood through adolescence. Learn more about HIDS symptoms on this page of our comparative/chart database at autoinflammatory-search.org.

Amyloidosis is not often seen in HIDS. There is a more severe condition, known as Mevalonate Aciduria (MA) that also involves a mutation in the MVK gene, but it is associated with significant, chronic inflammation, dysmorphic facial features, failure to thrive,systemic organ involvement and neurocognitive delays. Please refer to our autoinflammatory-search.org chart/database for a full description of MA.

Watch this video by Dr Anna Simon, leading expert on MKD/HIDS from the 2019 NIH-WRNMMC 2nd Symposium on Autoinflammatory and Immunedysregulatory Diseases to learn more about diagnosis and treatment for this rare autoinflammatory disease.

Visit our blog for a more detailed discussion on HIDS, along with references at saidsupport.org HIDS info

Compare HIDS to PFAPA, a different autoinflammatory disease on our saidsupport.org blog.