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Rheumatology 2001; 40: 579-584
© 2001 British Society for Rheumatology
Paediatric Rheumatology |
Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D
Paediatric Rheumatology/Series Editor: P. Woo
Departments of General Paediatrics,
2 Paediatric Immunology and
3 Metabolic Disorders, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, Departments of
1 Clinical Chemistry and Paediatrics and
4 Paediatric Immunology, Emma Children's Hospital, Academic Medical Centre, Amsterdam and
5 Department of Paediatric Rheumatology, Beatrix Children's Clinic, Academic Hospital Groningen, The Netherlands
Abstract
Objectives. The hyperimmunoglobulinaemia D and periodic fever syndrome (HIDS) was found recently to be caused by a deficiency of mevalonate kinase (MK). The aim of this study was to examine whether a relationship exists between the clinical expression of HIDS and the extent of MK deficiency.
Methods. The medical records of children diagnosed with HIDS were reviewed for clinical features and serum immunoglobulin values. The mevalonic acid excretion in urine and MK enzyme activity in patients' cells were measured and the cDNA of the MVK gene was sequenced.
Results. Fifteen patients with recurrent fever and raised serum immunoglobulin (Ig) D were included. Their clinical features varied. Eleven patients had a deficiency of MK, caused by mutations in the MVK gene. One mutation (V377I) was common to all 11 patients. Nine patients were compound heterozygotes for V377I and various other MVK mutations. There was no apparent relationship between the observed mutations and the clinical features. Surprisingly, four boys had normal MK activity and no MVK mutations.
Conclusions. Most HIDS patients have mutations in the MVK gene. The clinical variability observed cannot be explained by genotypic differences. Periodic fever and elevated IgD can result from other, still unknown, causes. Hence, testing for MK deficiency is necessary in patients with unexplained periodic fever.
KEY WORDS: Familial Mediterranean Fever, Fever, Hypergammaglobulinaemia, IgD, Mevalonate kinase, Mevalonic acid, Periodicity.
Notes
Correspondence to: J. Frenkel, Department of General Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Home mailbox KE.04.133.1, P.O. Box 85090, 3508AB Utrecht, The Netherlands.
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