RSS Feeds
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; and
- for the International HIDS Study Group
- 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.
Abstract
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.
Article and Author Information
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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.
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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.
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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{at}worldonline.nl.
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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.
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Drs. Cuisset and Delpech: Génétique et Physiopathologie des Maladies Inflammatoires Héréditaires, INSERM EMI 00-05, Hôpital Cochin, Paris 75014, France.
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Dr. Vincent: Groupe de Recherches Métaboliques, ICP and Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, B-1200 Brussels, Belgium.
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Author Contributions: Conception and design: A. Simon, L. Cuisset, J.W.M. van der Meer, J.P.H. Drenth.
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Analysis and interpretation of the data: A. Simon, M.-F. Vincent, J.P.H. Drenth.
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Drafting of the article: A. Simon, J.P.H. Drenth.
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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.
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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.
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Provision of study materials or patients: S.D. van der Velde-Visser, J.W.M. van der Meer, J.P.H. Drenth.
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Statistical expertise: A. Simon.
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Obtaining of funding: J.W.M. van der Meer, J.P.H. Drenth.
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Administrative, technical, or logistic support: M.-F. Vincent, S.D. van der Velde-Visser.
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Collection and assembly of data: A. Simon.
- Copyright ©2004 by the American College of Physicians
