Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Hyper-IgD And Periodic Fever Syndrome (HIDS) [R77.1]

OMIM numbers: 260920, 251170 (MVK)

Dr. rer. nat. Barbara Bangol, Dr. med. Kaimo Hirv

Scientific Background

The hyper-IgD syndrome (hyperimmunoglobulinemia D and periodic fever syndrome, HIDS) is one of the rare hereditary periodic fever syndromes. It is estimated that there are some hundreds HIDS cases worldwide. Inheritance is autosomal recessive. Almost unexceptionally, HIDS manifests in early childhood, frequently already within the first year of life. The episodes of fever usually occur every 4–8 weeks and last approx. 3–7 days. They are typically accompanied by cervical lymphadenopathy, arthritis/arthralgia, exanthema resembling measles as well as abdominal pain with diarrhea and vomiting. Frequently, the fever is preceded by severe headache and shivering. Development of amyloidosis is very rare. In most cases, the IgD (and IgA) serum concentration is continuously elevated to more than 100 IU/ml; however, in approx. 20% of all cases, especially young children, the IgD levels may be within the norm. Currently, there are no recognized guidelines for the treatment of HIDS. Besides non-steroidal antiphlogistics, corticosteroids are currently in use during the fever attacks.

The disease is caused by mutations (especially missense mutations) in the MVK gene, which encodes the mevalonate kinase, a key enzyme of the cholesterol biosynthesis. The association between the defect in the cholesterol biosynthesis and the autoinflammatory clinical picture has so far not been clarified. Mutations associated with HIDS lead to a decrease in enzyme activity, while mutations that cause a complete loss of function result in the severe clinical picture of mevalonic aciduria. Approximately 80% of all HIDS patients have the mutation V377I in exon 11 in the homozygous state or in combination with another mutation.