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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

Anna Simon, MD; Laurence Cuisset, PhD; M.-Françoise Vincent, PhD; Saskia D. van der Velde-Visser, PhD; Marc Delpech, PhD; Jos W.M. van der Meer, MD, PhD; Joost P.H. Drenth, MD, PhD, International HIDS Study Group
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From University Medical Center St. Radboud, Nijmegen, the Netherlands; Génétique et Physiopathologie des Maladies Inflammatoires Héréditaires and Hôpital Cochin, Paris, France; and Université Catholique de Louvain, Brussels, Belgium.

Acknowledgments: The authors thank the following members of the International Hyper-IgD Study Group for their role in blood collection: M. van Deuren, J.W.J. Bijlsma, R.J. Powell, C.M.R. Weemaes, J. Louis, T. Espanol, A. Metton, D. Jíilek, J. Mydlil, S. Kynclova, V. Kredbova, C.D.A. Stehouwer, W. Kuis, and A.M. Prieur.

Grant Support: Dr. Simon is a recipient of a Dutch Organization for Scientific Research Fellowship for Clinical Investigators (NWO no. 920-03-116). Dr. Drenth is an investigator of the Royal Dutch Academy of Arts and Sciences.

Requests for Single Reprints: Anna Simon, MD, Division of General Internal Medicine, 541, University Medical Center St. Radboud, Box 9101, 6500 HB Nijmegen, the Netherlands; e-mail, a.simon@worldonline.nl.

Current Author Addresses: Drs. Simon, van der Velde-Visser, van der Meer, and Drenth: University Medical Center St. Radboud, Box 9101, 6500 HB Nijmegen, the Netherlands.

Drs. Cuisset and Delpech: Génétique et Physiopathologie des Maladies Inflammatoires Héréditaires, INSERM EMI 00-05, Hôpital Cochin, Paris 75014, France.

Dr. Vincent: Groupe de Recherches Métaboliques, ICP and Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, B-1200 Brussels, Belgium.

Author Contributions: Conception and design: A. Simon, L. Cuisset, J.W.M. van der Meer, J.P.H. Drenth.

Analysis and interpretation of the data: A. Simon, M.-F. Vincent, J.P.H. Drenth.

Drafting of the article: A. Simon, J.P.H. Drenth.

Critical revision of the article for important intellectual content: A. Simon, L. Cuisset, M. Delpech, J.W.M. van der Meer, J.P.H. Drenth.

Final approval of the article: A. Simon, L. Cuisset, M.-F. Vincent, S.D. van der Velde-Visser, M. Delpech, J.W.M. van der Meer, J.P.H. Drenth.

Provision of study materials or patients: S.D. van der Velde-Visser, J.W.M. van der Meer, J.P.H. Drenth.

Statistical expertise: A. Simon.

Obtaining of funding: J.W.M. van der Meer, J.P.H. Drenth.

Administrative, technical, or logistic support: M.-F. Vincent, S.D. van der Velde-Visser.

Collection and assembly of data: A. Simon.

Ann Intern Med. 2001;135(5):338-343. doi:10.7326/0003-4819-135-5-200109040-00010
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Background: The hyper-IgD and periodic fever syndrome (HIDS) is characterized by recurrent attacks of fever, abdominal distress, and arthralgia and is caused by mevalonate kinase mutations.

Objective: To ascertain the role of mevalonate kinase and the usefulness of molecular diagnosis in HIDS.

Design: Cross-sectional study.

Setting: The international Nijmegen HIDS registry.

Patients: 54 patients from 41 families who met the clinical criteria for HIDS.

Measurements: Clinical symptoms and signs, immunoglobulin concentration, leukocyte count, erythrocyte sedimentation rate, mutation analysis, and mevalonate kinase enzyme activity assay.

Results: There were two groups of patients: 41 patients with mevalonate kinase mutations (classic-type HIDS) and 13 patients without mutations (variant-type HIDS). Patients with classic-type HIDS had a lower mevalonate kinase enzyme activity, a higher IgD level, and more additional symptoms with attacks. The IgD level did not correlate with disease severity, mevalonate kinase enzyme activity, or genotype.

Conclusion: Genetic heterogeneity exists among patients with a clinical diagnosis of HIDS.


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Mevalonate kinase enzyme activity and IgD levels in patients with classic-type or variant-type hyper-IgD and periodic fever syndrome (HIDS).Top.squarescirclesBottom.

Mevalonate kinase enzyme activity, as measured in lymphoblasts, in patients with classic-type ( ) and variant-type ( ) HIDS. The horizontal bars represent the mean. Serum level of IgD in patients with classic-type versus variant-type HIDS. Horizontal bars represent the median of the groups. Normal range in healthy persons for serum IgD level is <100 kIU/L.

Grahic Jump Location




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Summary for Patients

Can Genetics Help Diagnose the Hyper-IgD and Periodic Fever Syndrome?

The summary below is from the full report 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.


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