1/9. Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) in a child with normal serum IgD, but increased serum IgA concentration.This report describes a boy with hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). The serum IgD level was normal, but the serum IgA concentration was markedly elevated. In addition, he had a history of orchitis on two occasions, a previously unreported manifestation of HIDS. This report expands the clinical and laboratory features associated with HIDS and serves to emphasize that a normal serum IgD level does not exclude the diagnosis of HIDS.- - - - - - - - - - ranking = 1keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
2/9. Favorable preliminary experience with etanercept in two patients with the hyperimmunoglobulinemia D and periodic fever syndrome.OBJECTIVE: The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM 260920) is caused by recessive mutations in the mevalonate kinase gene (MVK), which encodes an enzyme involved in cholesterol and nonsterol isoprenoid biosynthesis. HIDS is characterized by persistently elevated polyclonal IgD and recurrent febrile episodes. Although abnormalities in tumor necrosis factor alpha (TNF alpha) are not the primary cause of HIDS, plasma TNF alpha levels are elevated in HIDS patients during attacks and thus may be a therapeutic target. This study assessed the effects of etanercept, a soluble p75 TNF alpha receptor-Fc fusion protein, in 2 patients with HIDS. methods: We performed biochemical and molecular genetic analyses on 2 girls with periodic episodes of fever, skin rash, abdominal pain, and arthralgia, of whom 1 had elevated levels of serum IgD. After the diagnosis of HIDS was made, treatment with etanercept was initiated in both patients. Clinical response was recorded in a standardized diary, and serum levels of cytokines and their decoy receptors were serially measured in 1 of the 2 patients. RESULTS: Urinary mevalonate levels were elevated in both girls. Patient 1 was heterozygous for a known MVK missense mutation (V377I) and a novel mutation that led to skipping of exon 3. Patient 2 was found to have V377I and a new missense mutation, S329R. Neither patient had mutations in TNFRSF1A or MEFV, the genes for the TNF receptor-associated periodic syndrome and familial mediterranean fever, respectively. Etanercept reduced the frequency and severity of symptoms in both patients, whereas the levels of serum IgD and urine mevalonate remained unchanged. CONCLUSION: Our favorable experience with etanercept for the treatment of HIDS suggests that further investigation of this therapy is warranted.- - - - - - - - - - ranking = 5keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
3/9. First report of systemic reactive (AA) amyloidosis in a patient with the hyperimmunoglobulinemia D with periodic fever syndrome.Systemic reactive (AA) amyloidosis, leading to renal failure, is a severe complication of most hereditary periodic fever syndromes. The risk of developing this life-threatening condition varies widely among these disorders, being higher for patients affected by familial mediterranean fever and tumor necrosis factor receptor-associated periodic syndrome. In spite of an acute-phase response during attacks, amyloidosis has never, to date, been described in patients affected with the hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). This is the first report to describe the occurrence of renal AA amyloidosis causing severe nephrotic syndrome in a young Italian man affected with HIDS. The diagnosis of HIDS was established according to clinical, laboratory, and genetic criteria as required by the international Nijmegen HIDS registry. In this patient, 2 mutations in the mevalonate kinase gene were identified, one of which, the leucine-to-arginine substitution at codon 265, is novel.- - - - - - - - - - ranking = 5keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
4/9. Identification of a novel mevalonate kinase gene mutation in combination with the common MVK V377I substitution and the low-penetrance TNFRSF1A R92Q mutation.The hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) is an autosomal recessively inherited autoinflammatory disease caused by mutations in the mevalonate kinase (MVK) gene on chromosome 12q24, which lead to a depressed enzymatic activity of mevalonate kinase (MK). TNF-receptor associated periodic syndrome (TRAPS), on the other hand, is the most frequent autosomal dominantly inherited periodic fever syndrome due to mutations in exons 2-4 and 6 of the TNFRSF1A gene on chromosome 12p13.2. We describe a girl with heterozygosity for the common MVK V377I mutation and for a novel T(1132) --> C transition, leading to the exchange of serine (TCC) by proline (CCC) at amino-acid position 378. Interestingly, our patient presented only with mild clinical features typical of HIDS and slightly increased immunoglobulin d levels, but a distinctly diminished MK activity. The girl was also heterozygous for the TNFRSF1A R92Q low-penetrance mutation, which may have significant proinflammatory effects. However, at the time of presentation, the patient had no TRAPS-associated symptoms.- - - - - - - - - - ranking = 1keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
5/9. Henoch-Schonlein purpura in a child with hyperimmunoglobulinemia D and periodic fever syndrome.This report describes a 3-year-old girl with a long history of periodic fever who presented with Henoch-Schonlein purpura. She was diagnosed with hyperimmunoglobulinemia D and periodic fever syndrome by means of mutation analysis of the mevalonate kinase gene. The serum IgA concentration was markedly elevated, but the serum IgD concentration was normal. This report emphasizes that Henoch-Schonlein purpura may be an important clinical feature of hyperimmunoglobulinemia D and periodic fever syndrome. In addition, this syndrome should be considered in patients with Henoch-Schonlein purpura in whom there is a history of recurrent fevers, even when the serum IgD concentration is normal.- - - - - - - - - - ranking = 6keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
6/9. Pseudodominant inheritance of the hyperimmunoglobulinemia D with periodic fever syndrome in a mother and her two monozygotic twins.Hyperimmunoglobulinemia D with periodic fever syndrome (HIDS) is a recessively inherited recurrent fever syndrome. We describe a family of 2 monozygotic twins and their mother with characteristic symptoms of HIDS, but normal levels of IgD and IgA, and with a dominant inheritance pattern. Mevalonate kinase (MK) activity was deficient in both children, and analysis of the MVK gene revealed compound heterozygosity for 2 new mutations, G25G and R277H. Being positioned adjacent to a donor splice site, the G25G mutation was shown by reverse transcription-polymerase chain reaction analyses to cause aberrant splicing of the MVK messenger rna, thus being disease-relevant. The mother, who was also symptomatic during her childhood and adolescence, was a compound heterozygote for I268T and R277H. Our findings expand the genetic and ethnic spectrum of HIDS and show that the possible presence of this disease cannot be excluded based solely on inheritance patterns. In each case in which HIDS is clinically suspected, analysis of MK activity and/or the MVK gene (especially exons 9 and 11) should be performed.- - - - - - - - - - ranking = 4keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
7/9. AA amyloidosis complicating hyperimmunoglobulinemia D with periodic fever syndrome: a report of two cases.AA amyloidosis is the most serious potential complication of the inherited autoinflammatory syndromes and frequently results in end-stage renal failure. Although this complication is well recognized in familial mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, and Muckle-Wells syndrome, there is only 1 previous published report of its occurrence in hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). We report 2 further cases of patients with AA amyloidosis in HIDS, both of whom developed dialysis-dependent renal failure, and we describe the outcome of the first renal transplant in this setting.- - - - - - - - - - ranking = 5keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
8/9. Hereditary periodic fever with systemic amyloidosis: is hyper-IgD syndrome really a benign disease?We report a case of amyloidosis in association with hyperimmunoglobulinemia D syndrome (HIDS). The patient showed typical clinical features of HIDS. He had crescentic glomerulonephritis progressing to end-stage renal disease at age 13 years. Eight years later, he developed an AA-type amyloidosis with extensive involvement of the intestine, respiratory tract, and thyroid gland. These unusual complications of HIDS seriously challenge the assumption that the disease is associated with a good prognosis.- - - - - - - - - - ranking = 1keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |
9/9. IgD immune complex vasculitis in a patient with hyperimmunoglobulinemia D and periodic fever.We describe a 27-year-old Dutch woman with the hyperimmunoglobulinemia D and periodic fever syndrome. During febrile attacks she occasionally presented with skin lesions on the distal parts of her upper and lower extremities, with the histologic picture of a leukocytoclastic vasculitis. Clear perivascular deposits of IgD and C3 were presented in early lesional skin on immunofluorescence investigation. Circulating IgD immune complexes were demonstrated on several occasions, both during and in between clinical attacks. These findings are consistent with an IgD immune complex-mediated pathogenesis for the skin lesions. In 10 patients with other forms of immune complex vasculitis of the skin, minimal perivascular deposits of IgD were found in four cases. In these cases, however, IgD was never found as the solitary immunoglobulin class.- - - - - - - - - - ranking = 5keywords = hyperimmunoglobulinemia (Clic here for more details about this article) |