MCID: HYP088
MIFTS: 49

Hyper-Igd Syndrome

Categories: Genetic diseases, Rare diseases, Bone diseases, Skin diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Hyper-Igd Syndrome

MalaCards integrated aliases for Hyper-Igd Syndrome:

Name: Hyper-Igd Syndrome 53 72 49 55 13 51
Hyperimmunoglobulinemia D and Periodic Fever Syndrome 53 49 71
Hids 53 55 71
Hyperimmunoglobulinemia D with Periodic Fever 55
Hyperimmunoglobinemia D with Recurrent Fever 55
Partial Mevalonate Kinase Deficiency 55
Hyperimmunoglobulinemia D Syndrome 55
Deficiency of Mevalonate Kinase 69
Periodic Fever, Dutch Type 53
Periodic Fever Dutch Type 49
Hyperimmunoglobulinemia D 69
Hyper Igd Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
hyperimmunoglobulinemia d with periodic fever
Inheritance: Autosomal recessive; Age of onset: Infancy;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
prodromal symptoms include nasal congestion, dry throat, severe fatigue, vertigo, and headache
recurrent febrile crises preceded by chills and accompanied by headache and bilateral cervical lymphadenopathy
febrile attacks disappear in adulthood in some patients
onset of symptoms less than one year
allelic to mevalonic aciduria
length of attack, 3 to 7 days
frequency of attack, monthly - bimonthly


HPO:

31
hyper-igd syndrome:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hyper-Igd Syndrome

NIH Rare Diseases : 49 Hyper IgD syndrome is the less severe form of a metabolic disorder known as mevalonate kinase deficiency. It is considered an auto-inflammatory disease, with recurrent episodic or chronic unexplained inflammation, characterized by periodic episodes of fever, and other symptoms such as joint pain, swollen lymph nodes, skin rash, headaches, and abdominal pain. Most episodes last several days and occur periodically throughout life. The frequency of episodes and their severity vary greatly from person to person. These attacks can occur spontaneously or be triggered by vaccinations, infections, and/or emotional or physical stress. Growth and development is usually not affected. Hyper IgD syndrome is caused by mutations in the MVK gene which provides instructions for making the mevalonate kinase enzyme. The mutations result in the partial deficiency of the enzyme. A more severe form of maevalonate kinase deficiency is known as mevalonic aciduria. It is inherited in an autosomal recessive manner. Treatment is with anakinra, and other medications, but not all patients show a complete response. In most cases, the frequency of the disease's episodes decreases over time.  Last updated: 6/26/2017

MalaCards based summary : Hyper-Igd Syndrome, also known as hyperimmunoglobulinemia d and periodic fever syndrome, is related to mevalonic aciduria and brucellosis, and has symptoms including ataxia, arthralgia and myalgia. An important gene associated with Hyper-Igd Syndrome is MVK (Mevalonate Kinase), and among its related pathways/superpathways are Innate Immune System and Interleukin-10 signaling. The drugs Antibodies, Monoclonal and Immunoglobulins have been mentioned in the context of this disorder. Affiliated tissues include skin, lymph node and bone.

UniProtKB/Swiss-Prot : 71 Hyperimmunoglobulinemia D and periodic fever syndrome: Autosomal recessive disease characterized by recurrent episodes of unexplained high fever associated with skin rash, diarrhea, adenopathy (swollen, tender lymph nodes), arthralgias and/or arthritis. Concentration of IgD, and often IgA, are above normal.

Wikipedia : 72 Hyperimmunoglobulinemia D with recurrent fever (HIDS) is a periodic fever syndrome originally described... more...

Description from OMIM: 260920

Related Diseases for Hyper-Igd Syndrome

Diseases related to Hyper-Igd Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 38)
# Related Disease Score Top Affiliating Genes
1 mevalonic aciduria 32.6 IL1RN MVK
2 brucellosis 30.4 CRP IL1RN
3 periodic fever, familial, autosomal dominant 29.8 MVK TNFRSF1A
4 pericarditis 29.7 CRP TNFRSF1A
5 amyloidosis 29.3 SAA1 TNFRSF1A
6 familial mediterranean fever 28.5 CRP IL1RN MVK SAA1 TNFRSF1A
7 ichthyosis, hystrix-like, with deafness 11.7
8 kid syndrome 11.4
9 cryopyrin-associated periodic syndrome 10.1 CRP IL1RN
10 acute cholangitis 10.1 CRP IL1RN
11 cinca syndrome 10.1 IL1RN MVK
12 cartilage disease 10.1 CRP IL1RN
13 nutritional deficiency disease 10.1 CRP MVK
14 adult-onset still's disease 10.1 CRP IL1RN
15 bronchus cancer 10.1 CRP SAA1
16 amyloidosis aa 10.0 CRP SAA1
17 temporal arteritis 10.0 CRP IL1RN
18 autoinflammation, lipodystrophy, and dermatosis syndrome 10.0 CRP IL1RN
19 bone inflammation disease 10.0 CRP IL1RN
20 juvenile rheumatoid arthritis 10.0 CRP IL1RN
21 glomerulonephritis 10.0
22 keratopathy 10.0
23 crescentic glomerulonephritis 10.0
24 synovitis 9.9 CRP IL1RN
25 pericoronitis 9.9 CRP TNFRSF1A
26 periodontal disease 9.9 CRP IL1RN
27 muckle-wells syndrome 9.9 CRP TNFRSF1A
28 wells syndrome 9.9 CRP TNFRSF1A
29 palindromic rheumatism 9.9 CRP TNFRSF1A
30 pericardial effusion 9.9 CRP TNFRSF1A
31 amyloidosis, familial visceral 9.7 SAA1 TNFRSF1A
32 psoriatic arthritis 9.6 CRP TNFRSF1A
33 relapsing fever 9.6 CRP MVK TNFRSF1A
34 exanthem 9.5 CRP IL1RN TNFRSF1A
35 spondyloarthropathy 1 9.5 CRP IL1RN TNFRSF1A
36 behcet syndrome 9.5 CRP IL1RN TNFRSF1A
37 inflammatory bowel disease 9.2 CRP IL1RN TNFRSF1A
38 rheumatoid arthritis 9.1 CRP IL1RN SAA1 TNFRSF1A

Graphical network of the top 20 diseases related to Hyper-Igd Syndrome:



Diseases related to Hyper-Igd Syndrome

Symptoms & Phenotypes for Hyper-Igd Syndrome

Symptoms via clinical synopsis from OMIM:

53
Neurologic Central Nervous System:
headache

Skeletal Limbs:
arthritis
arthralgias

Hematology:
neutrophilia
leukocytosis (mean leukocyte count 18.7 x 10(9)/l)

Skin Nails Hair Skin:
rash (erythematous macules or papules)

Laboratory Abnormalities:
mildly elevated urinary mevalonic acid
elevated erythrocyte sedimentation rate (mean 90mm/h)

Abdomen Gastroin testinal:
abdominal pain
vomiting
diarrhea

Head And Neck Eyes:
optic disc pallor
night blindness
attenuated retinal vessels
retinitis pigmentosa (in some patients)
visual field loss
more
Abdomen Spleen:
splenomegaly (in childhood)

Immunology:
elevated polyclonal igd (equal to or greater than 100 iu/ml)
elevated iga (equal to or greater than 2.6g/l)
lymphadenopathy (cervical, inguinal, axillary)


Clinical features from OMIM:

260920

Human phenotypes related to Hyper-Igd Syndrome:

55 31 (show all 37)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 occasional (7.5%) Occasional (29-5%) HP:0001251
2 arthralgia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002829
3 myalgia 55 31 hallmark (90%) Very frequent (99-80%) HP:0003326
4 seizures 55 31 occasional (7.5%) Occasional (29-5%) HP:0001250
5 abdominal pain 55 31 hallmark (90%) Very frequent (99-80%) HP:0002027
6 diarrhea 55 31 frequent (33%) Frequent (79-30%) HP:0002014
7 global developmental delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001263
8 arthritis 55 31 frequent (33%) Frequent (79-30%) HP:0001369
9 hepatomegaly 55 31 hallmark (90%) Very frequent (99-80%) HP:0002240
10 acrocyanosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001063
11 limitation of joint mobility 55 31 occasional (7.5%) Occasional (29-5%) HP:0001376
12 growth delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001510
13 migraine 55 31 frequent (33%) Frequent (79-30%) HP:0002076
14 intestinal obstruction 55 31 occasional (7.5%) Occasional (29-5%) HP:0005214
15 purpura 55 31 occasional (7.5%) Occasional (29-5%) HP:0000979
16 gastrointestinal hemorrhage 55 31 hallmark (90%) Very frequent (99-80%) HP:0002239
17 erythema 55 31 occasional (7.5%) Occasional (29-5%) HP:0010783
18 urticaria 55 31 frequent (33%) Frequent (79-30%) HP:0001025
19 vasculitis 55 31 frequent (33%) Frequent (79-30%) HP:0002633
20 papule 55 31 frequent (33%) Frequent (79-30%) HP:0200034
21 lymphadenopathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0002716
22 peritonitis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002586
23 recurrent aphthous stomatitis 55 31 frequent (33%) Frequent (79-30%) HP:0011107
24 elevated erythrocyte sedimentation rate 55 31 hallmark (90%) Very frequent (99-80%) HP:0003565
25 increased iga level 55 31 hallmark (90%) Very frequent (99-80%) HP:0003261
26 episodic fever 55 31 hallmark (90%) Very frequent (99-80%) HP:0001954
27 headache 31 HP:0002315
28 vertigo 31 HP:0002321
29 vomiting 31 HP:0002013
30 splenomegaly 31 HP:0001744
31 nyctalopia 31 HP:0000662
32 leukocytosis 31 HP:0001974
33 skin rash 31 HP:0000988
34 hypermelanotic macule 31 HP:0001034
35 rod-cone dystrophy 31 occasional (7.5%) HP:0000510
36 optic disc pallor 31 HP:0000543
37 neutrophilia 31 HP:0011897

UMLS symptoms related to Hyper-Igd Syndrome:


vomiting, headache, diarrhea, arthralgia, abdominal pain

Drugs & Therapeutics for Hyper-Igd Syndrome

Drugs for Hyper-Igd Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Antibodies, Monoclonal Phase 3,Phase 2
2 Immunoglobulins Phase 3,Phase 2
3 Antibodies Phase 3,Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis or Hereditary Periodic Fevers Who Participated in the CACZ885G2301E1, CACZ885G2306 or CACZ885N2301 Studies Active, not recruiting NCT02334748 Phase 3 canakinumab
2 Canakinumab in Patients With Active Hyper-IgD Syndrome Completed NCT01303380 Phase 2 Canakinumab
3 B7 Coreceptor Molecules in Hyper IgD Syndrome Form of Mevalonate Kinase Deficiency Unknown status NCT01568736
4 Familial Mediterranean Fever and Related Disorders: Genetics and Disease Characteristics Recruiting NCT00001373

Search NIH Clinical Center for Hyper-Igd Syndrome

Genetic Tests for Hyper-Igd Syndrome

Anatomical Context for Hyper-Igd Syndrome

MalaCards organs/tissues related to Hyper-Igd Syndrome:

38
Skin, Lymph Node, Bone, Monocytes

Publications for Hyper-Igd Syndrome

Articles related to Hyper-Igd Syndrome:

(show all 38)
# Title Authors Year
1
The challenge of autoinflammatory syndromes: with an emphasis on hyper-IgD syndrome. ( 27856657 )
2016
2
Amyloid A amyloidosis secondary to hyper IgD syndrome and response to IL-1 blockage therapy. ( 26819362 )
2016
3
Mevalonate kinase deficiency (hyper-IgD syndrome) overlap mutation familial Mediterranean fever. ( 27079959 )
2016
4
Anti-interleukin 6 receptor therapy for hyper-IgD syndrome. ( 26516243 )
2015
5
Hyper-IgD syndrome/mevalonate kinase deficiency: what is new? ( 25990874 )
2015
6
Treatment of adult hyper-IgD syndrome with canakinumab. ( 26116953 )
2015
7
Overlap of Familial Mediterranean Fever and Hyper-IgD Syndrome in an Arabic Kindred. ( 25708585 )
2015
8
Long chain fatty acid (Lcfa) abnormalities in hyper Igd syndrome (Hids) and Familial Mediterranean Fever (Fmf): new insight into heritable periodic fevers. ( 23375471 )
2013
9
Mevalonate kinase deficiency (hyper IgD syndrome with periodic fever)--different faces with separate treatments: two cases and review of the literature. ( 23692791 )
2012
10
Renal amyloidosis due to hyper-IgD syndrome. ( 23169386 )
2012
11
Aberrant expression of costimulatory molecules in splenocytes of the mevalonate kinase-deficient mouse model of human hyper-IgD syndrome (HIDS). ( 21607759 )
2012
12
Hyper-IgD syndrome or mevalonate kinase deficiency. ( 21760510 )
2011
13
A novel mutation in TNFRSF1A associated with overlapping features of tumor necrosis factor receptor-associated periodic syndrome and hyper-IgD syndrome. ( 20346247 )
2010
14
Hyper-IgD syndrome with novel mutation in a Japanese girl. ( 18941711 )
2009
15
Recurrent pericarditis in hyper-IgD syndrome. ( 19772809 )
2009
16
Nummular keratopathy in a patient with Hyper-IgD Syndrome. ( 19656398 )
2009
17
A patient with hyper-IgD syndrome responding to simvastatin treatment. ( 19046710 )
2008
18
[MVK gene abnormality and new approach to treatment of hyper IgD syndrome and periodic fever syndrome]. ( 17473510 )
2007
19
Diagnostic value of serum immunoglobulinaemia D level in patients with a clinical suspicion of hyper IgD syndrome. ( 17804452 )
2007
20
A patient with hyper-IgD syndrome responding to anti-TNF treatment. ( 17171314 )
2007
21
Deletion of a single mevalonate kinase (Mvk) allele yields a murine model of hyper-IgD syndrome. ( 18008182 )
2007
22
Hereditary periodic fever with systemic amyloidosis: is hyper-IgD syndrome really a benign disease? ( 16931207 )
2006
23
Diagnostic challenge of hyper-IgD syndrome in four children with inflammatory gastrointestinal complaints. ( 16635911 )
2006
24
Effect of etanercept and anakinra on inflammatory attacks in the hyper-IgD syndrome: introducing a vaccination provocation model. ( 16093577 )
2005
25
Serum amyloid A serum concentrations and genotype do not explain low incidence of amyloidosis in Hyper-IgD syndrome. ( 16011988 )
2005
26
Effect of inflammatory attacks in the classical type hyper-IgD syndrome on immunoglobulin D, cholesterol and parameters of the acute phase response. ( 15324368 )
2004
27
A patient with hyper-IgD syndrome in Antalya, Turkey. ( 15045637 )
2004
28
Inefficacy of etanercept in a child with hyper-IgD syndrome and periodic fever. ( 15638064 )
2004
29
Hyper IgD syndrome (HIDS) associated with in vitro evidence of defective monocyte TNFRSF1A shedding and partial response to TNF receptor blockade with etanercept. ( 12452839 )
2002
30
Mevalonic aciduria and hyper-IgD syndrome: two sides of the same coin? ( 11486910 )
2001
31
Non-steroidal anti-inflammatory drugs in the treatment of hyper-IgD syndrome. ( 11534513 )
2001
32
Hyper-IgD syndrome and familial Hibernian fever are true periodic fever syndromes. ( 10969277 )
2000
33
[Identification of the gene for hyper-IgD syndrome: a model of modern genetics]. ( 10800545 )
2000
34
Crescentic glomerulonephritis in hyper IgD syndrome. ( 10229000 )
1999
35
Hyper-IgD syndrome and pregnancy. ( 8886712 )
1996
36
Unstimulated peripheral blood mononuclear cells from patients with the hyper-IgD syndrome produce cytokines capable of potent induction of C-reactive protein and serum amyloid A in Hep3B cells. ( 8683144 )
1996
37
Clinical and immunological follow-up in children with hyper-IgD syndrome. ( 8167736 )
1993
38
Hyper-IGD syndrome: a new case treated with colchicine. ( 3229086 )
1988

Variations for Hyper-Igd Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Hyper-Igd Syndrome:

71 (show all 21)
# Symbol AA change Variation ID SNP ID
1 MVK p.His20Pro VAR_004022 rs104895295
2 MVK p.Pro167Leu VAR_004023 rs104895300
3 MVK p.Ile268Thr VAR_004024 rs104895304
4 MVK p.Val377Ile VAR_004027 rs28934897
5 MVK p.Val310Met VAR_009068 rs104895319
6 MVK p.His20Asn VAR_010956 rs11544299
7 MVK p.Leu39Pro VAR_010957 rs104895296
8 MVK p.Ser135Leu VAR_010959 rs104895297
9 MVK p.Ala148Thr VAR_010960 rs104895298
10 MVK p.Ser150Leu VAR_010961 rs747116992
11 MVK p.Gly202Arg VAR_010962 rs104895301
12 MVK p.Arg215Gln VAR_010963 rs104895303
13 MVK p.Gly309Ser VAR_010967 rs104895305
14 MVK p.Gly326Arg VAR_010968 rs104895308
15 MVK p.His20Gln VAR_029519 rs104895335
16 MVK p.Val132Ile VAR_029520 rs104895336
17 MVK p.Gly171Arg VAR_029521 rs104895337
18 MVK p.Gly211Glu VAR_029522 rs104895325
19 MVK p.Val250Ile VAR_029523 rs104895339
20 MVK p.Leu265Arg VAR_029524 rs104895316
21 MVK p.Gly376Val VAR_029527 rs104895340

ClinVar genetic disease variations for Hyper-Igd Syndrome:

6 (show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 MVK NM_000431.3(MVK): c.1129G> A (p.Val377Ile) single nucleotide variant Pathogenic rs28934897 GRCh37 Chromosome 12, 110034320: 110034320
2 MVK NM_000431.3(MVK): c.1000G> A (p.Ala334Thr) single nucleotide variant Pathogenic rs104895317 GRCh37 Chromosome 12, 110032947: 110032947
3 MVK NM_000431.3(MVK): c.59A> C (p.His20Pro) single nucleotide variant Pathogenic rs104895295 GRCh37 Chromosome 12, 110012686: 110012686
4 MVK NM_000431.3(MVK): c.803T> C (p.Ile268Thr) single nucleotide variant Pathogenic rs104895304 GRCh37 Chromosome 12, 110029080: 110029080
5 MVK NM_000431.3(MVK): c.494C> T (p.Pro165Leu) single nucleotide variant Pathogenic rs121917790 GRCh37 Chromosome 12, 110019322: 110019322
6 MVK NM_000431.3(MVK): c.928G> A (p.Val310Met) single nucleotide variant Pathogenic rs104895319 GRCh37 Chromosome 12, 110032875: 110032875
7 MVK NM_000431.3(MVK): c.16_34del19 (p.Leu6Glyfs) deletion Pathogenic rs104895334 GRCh38 Chromosome 12, 109574838: 109574856
8 MVK NM_000431.3(MVK): c.500C> T (p.Pro167Leu) single nucleotide variant Pathogenic/Likely pathogenic rs104895300 GRCh37 Chromosome 12, 110019328: 110019328
9 MVK NM_000431.3(MVK): c.604G> A (p.Gly202Arg) single nucleotide variant Pathogenic rs104895301 GRCh37 Chromosome 12, 110023903: 110023903
10 MVK NM_000431.3(MVK): c.417dupC (p.Gly140Argfs) duplication Pathogenic rs104895373 GRCh37 Chromosome 12, 110019245: 110019245
11 MVK NM_000431.3(MVK): c.72dupT (p.Gly25Trpfs) duplication Pathogenic rs104895322 GRCh37 Chromosome 12, 110012699: 110012699
12 MVK NM_000431.3(MVK): c.421dupG (p.Ala141Glyfs) duplication Pathogenic rs104895323 GRCh37 Chromosome 12, 110019249: 110019249
13 MVK NM_000431.3(MVK): c.1162C> T (p.Arg388Ter) single nucleotide variant Pathogenic rs104895360 GRCh37 Chromosome 12, 110034353: 110034353
14 MVK NM_000431.3(MVK): c.346T> C (p.Tyr116His) single nucleotide variant Pathogenic rs104895382 GRCh37 Chromosome 12, 110017726: 110017726
15 MVK NM_000431.3(MVK): c.442G> A (p.Ala148Thr) single nucleotide variant Pathogenic rs104895298 GRCh37 Chromosome 12, 110019270: 110019270
16 MVK NM_000431.3(MVK): c.564G> A (p.Trp188Ter) single nucleotide variant Pathogenic rs104895311 GRCh37 Chromosome 12, 110023863: 110023863
17 MVK NM_000431.3(MVK): c.608T> C (p.Val203Ala) single nucleotide variant Pathogenic rs104895332 GRCh37 Chromosome 12, 110023907: 110023907
18 MVK NM_000431.3(MVK): c.709A> T (p.Thr237Ser) single nucleotide variant Pathogenic rs104895366 GRCh37 Chromosome 12, 110028607: 110028607

Expression for Hyper-Igd Syndrome

Search GEO for disease gene expression data for Hyper-Igd Syndrome.

Pathways for Hyper-Igd Syndrome

Pathways related to Hyper-Igd Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.95 CRP IL1RN PTX3 SAA1 TNFRSF1A
2 10.31 IL1RN TNFRSF1A

GO Terms for Hyper-Igd Syndrome

Cellular components related to Hyper-Igd Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular region GO:0005576 9.35 CRP IL1RN PTX3 SAA1 TNFRSF1A
2 extracellular space GO:0005615 9.02 CRP IL1RN PTX3 SAA1 TNFRSF1A

Biological processes related to Hyper-Igd Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 acute-phase response GO:0006953 9.26 CRP SAA1
2 opsonization GO:0008228 9.16 CRP PTX3
3 negative regulation of inflammatory response GO:0050728 9.13 MVK SAA1 TNFRSF1A
4 inflammatory response GO:0006954 8.92 CRP IL1RN PTX3 TNFRSF1A

Molecular functions related to Hyper-Igd Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 virion binding GO:0046790 8.96 CRP PTX3
2 complement component C1q binding GO:0001849 8.62 CRP PTX3

Sources for Hyper-Igd Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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