Clinical and molecular variability in childhood periodic fever with hyperimmunoglobulinaemia D

被引:63
作者
Frenkel, J [1 ]
Houten, SM
Waterham, HR
Wanders, RJA
Rijkers, GT
Duran, M
Kuijpers, TW
van Luijk, W
Poll-The, BT
Kuis, W
机构
[1] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Gen Pediat, Home Mailbox KE 04-133-1,POB 85090, NL-3508 AB Utrecht, Netherlands
[2] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Paediat Immunol, NL-3508 AB Utrecht, Netherlands
[3] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Metab Disorders, NL-3508 AB Utrecht, Netherlands
[4] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Clin Chem, NL-1105 AZ Amsterdam, Netherlands
[5] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Paediat, NL-1105 AZ Amsterdam, Netherlands
[6] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, Dept Paediat Immunol, NL-1105 AZ Amsterdam, Netherlands
[7] Acad Hosp Groningen, Beatrix Children Clin, Dept Paediat Rheumatol, Groningen, Netherlands
关键词
familial Mediterranean fever; fever; hypergammaglobulinaemia; IgD; mevalonate kinase; mevalonic acid; periodicity;
D O I
10.1093/rheumatology/40.5.579
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:579 / 584
页数:6
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