Visit HIDS.net at:
http://www.hids.net/

and see the HIDS.net What is HIDS page at:
http://www.hids.net/patient/whatishids.html

For more scientific descriptions and links, go to:
http://www.diseasesdatabase.com/sieve/item1.asp?glngUserChoice=30161
or
http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?260920

Author:  Professor Gilles Grateau
Scientific editor:  Professor Loïc Guillevin
Date of creation:  March 1999
Updated:  July 2002: June 2003

-------------------------------------------------------------------------------

Name of the disease and its synonyms
Hyperimmunoglobulinemia D and periodic fever
Fever and hyperIgD syndrome
Hyper IgD syndrome (HIDS)
Dutch-type periodic fever

Excluded diseases
Familial Mediterranean fever
Recurrent autosomal dominant fever

Definition/Diagnostic criteria
The diagnosis is based on a group of clinical signs associated with a biochemical marker:  elevated serum concentration of IgD. This elevation is due to mevalonate kinese (MV) deficiency, MV is a key enzyme involved in cholesterol and nonsterol isoprene  biosynthesis.

Differential diagnosis
It includes a wide range of diseases that can be considered depending on the predominant clinical symptoms observed.

Incidence
It is unknown.

Clinical description
The hyperIgD and periodic fever syndrome is characterized by febrile attacks every 4–8 weeks associated with an intense inflammatory reaction, accompanied by adenopathies, abdominal pain, diarrhea, joint pain, hepatosplenomegaly and cutaneous signs.  The first attack usually occurs during infancy.

Management and treatments
This disease is difficult to treat.  Unlike familial Mediterranean fever, colchicine does not prevent attacks.  To control the symptoms of fever and pain many patients benefit from the use of non-specific drugs like paracetamol. Unfortunately, there is no other effective treatment at this moment.

Etiology
Mutations in the gene coding for mevalonate kinase (MVK) are responsible for the disease.  It is located at chromosome 12q24 and is subjected to autosomal recessive inheritance.  Mevalonate kinase deficiency is known and gives rise in children to a developmental disease called mevalonic aciduria.

Biological methods of diagnosis
The diagnosis is based on clearly elevated serum IgD concentrations, > 100 U/mL or 141 mg/L, during and between attacks. Increased IgD concentration is not
specific and can be observed in other inflammatory diseases: Familial Mediterranean fever, TRAPS, etc. The diagnosis can currently be confirmed by pathologic low activity of mevalonate kinase. It can be established by the detection of elevated excretions of mevalonic acid in urine during fever episodes or by dosage of level of mevalonate kinase in lymphocytes.

Unresolved questions and comments
The inflammatory mechanism of this metabolic disease remains to be discovered.

References

Van der Meer JWM, Vossen JM, Radl J et al. Hyperimmunoglobulinemia D and periodic fever: a new syndrome. Lancet 1984;1(8386): 1087-1090

Drenth JP, Haagsma CJ, van der Meer JW: Hyperimmunoglobulinemia D and periodic fever syndrome. The clinical spectrum in a series of 50 patients.
International Hyper-IgD Study Group. Medicine (Baltimore) 1994, 73:133-144

Drenth JP, Cuisset L, Grateau G, Vasseur C, van de Velde-Visser SD, de Jong JG, Beckmann JS, van der Meer JW, Delpech M: Mutations in the gene
encoding mevalonate kinase cause hyper-IgD and periodic fever syndrome. International Hyper-IgD Study Group. Nat Genet 1999, 22:178-181

Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT,
Waterham HR, Wanders RJ, Poll-The BT: Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever
syndrome. Nat Genet 1999, 22:175-177

Frenkel J, Houten SM, Waterham HR, Wanders RJ, Rijkers GT, Kimpen JL, Duran R, Poll-The BT, Kuis W. Mevalonate kinase deficiency and Dutch type periodic fever. Clin Exp Rheumatol. 2000;18: 525-532

Simon A, Cuisset L, Vincent MF, van Der Velde-Visser SD, Delpech M, van Der Meer JW, Drenth JP. Molecular analysis of the mevalonate kinase gene in a cohort of patients with the hyper-igd and periodic fever syndrome: its application as a diagnostic tool. Ann Intern Med. 2001;135 :338-43
--------------------------------------------------------------------------------

This paper should be referenced as such
Grateau G, Hyperimmunoglobulinemia D and periodic fever; Orphanet encyclopedia, July 2002:
http://orphanet.infobiogen.fr/data/patho/GB/uk-hyperIgD.html

--------------------------------------------------------------------------------

Address for correspondence:
Pr Gilles GRATEAU
Service de médecine interne
Hôtel-Dieu
1 Place du Parvis Notre-Dame
75181 PARIS CEDEX 4
FRANCE

The following article appears originally at:
http://www.annals.org/issues/v135n5/nts/200109040-00006.html

Can Genetics Help Diagnose the Hyper-IgD
and Periodic Fever Syndrome?
  
What is the problem and what is known about it so far?

Periodic fever is an uncommon condition defined by recurring bouts of fever in people who seem healthy except during their fever attacks. The condition is hard to diagnose because there are several types of periodic fever as well as multiple causes of recurring fevers. In 1984, researchers identified a type of periodic fever that they called the hyper-IgD and periodic fever syndrome (HIDS). People with HIDS have persistently high levels of an antibody known as immunoglobulin D (IgD). They have recurring bouts of high fever with swollen lymph nodes, abdominal distress (vomiting, diarrhea, and pain), and joint pain. Symptoms last for several days and recur every few weeks. Researchers think that the underlying cause of HIDS is a mutation of a specific gene (the mevalonate kinase gene). This mutation can be identified with special molecular genetic tests. Whether the tests can be used to diagnose HIDS is unclear, however.

Why did the researchers do this particular study?

To find out whether molecular genetic tests for mutations in the mevalonate kinase gene are useful for diagnosing HIDS.

Who was studied?

The researchers studied 54 patients with HIDS who were identified from a special registry in the Netherlands. All had repeated bouts of fever, with clinical findings such as swollen lymph glands, joint pain, skin rashes, or abdominal symptoms. The patients also had persistently high levels of IgD.

How was the study done?

The researchers analyzed cell samples and DNA obtained from patients' blood. They looked for mutations in the mevalonate kinase gene.

What did the researchers find?

Forty-one of the 54 patients with clinically diagnosed HIDS had mutations in their mevalonate kinase gene. The patients with the gene mutations had much higher IgD levels and more symptoms with their fever bouts than did the patients without mutations. They also more often had siblings with HIDS.

What were the limitations of the study?

Because the study did not include patients with other types of recurring or periodic fevers, it could not determine the usefulness of molecular genetic testing in distinguishing HIDS from other fever syndromes.

What are the implications of the study?

Mutations in the mevalonate kinase gene appear to be common among people with clinically diagnosed HIDS. However, because molecular genetic tests for these mutations are not always positive, they cannot be used to rule out the diagnosis of HIDS.

The full report is titled "Molecular Analysis of the Mevalonate Kinase Gene in a Cohort of Patients with the Hyper-IgD and Periodic Fever Syndrome: Its Application as a Diagnostic Tool." It is in the 4 September 2001 issue of Annals of Internal Medicine (volume 135, pages 338-343). The authors are A Simon, L Cuisset, M-F Vincent, SD van der Velde-Visser, M Delpech, JWM van der Meer, and JPH Drenth, for the International HIDS Study Group.  |Full Text|

Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine. Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. The summaries may be reproduced for not-for-profit educational purposes only. Any other uses must be approved by the American College of Physicians-American Society of Internal Medicine.

Copyright ©2003 American College of Physicians