MCID: HYP373
MIFTS: 30

Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

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

Aliases & Classifications for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

MalaCards integrated aliases for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

Name: Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive 53 13
Hyperimmunoglobulin E Recurrent Infection Syndrome, Autosomal Recessive 49 24 71 28
Ar-Hies 49 24 71
Combined Immunodeficiency Due to Dock8 Deficiency 24 55
Hyperimmunoglobulin E Syndrome Type 2 24 71
Dock8 Immunodeficiency Syndrome 24 55
Cid Due to Dock8 Deficiency 24 55
Hies Autosomal Recessive 49 71
Dock8 Deficiency 49 24
Combined Immunodeficiency Due to Dedicator of Cytokinesis 8 Protein Deficiency 55
Hyper Ige Recurrent Infection Syndrome, Autosomal Recessive 24
Hyper-Ige Recurrent Infection Syndrome Autosomal Recessive 71
Hyper Immunoglobulin E Syndrome, Autosomal Recessive 24
Hyper-Immunoglobulin E Syndrome, Autosomal Recessive 69
Hyper Ig E Syndrome, Autosomal Recessive 49
Hyper-Ige Syndrome, Autosomal Recessive 53
Autosomal Recessive Hyper Ige Syndrome 49
Autosomal Recessive Hyper-Ige Syndrome 24
Hyper-Ige Syndrome Autosomal Recessive 71
Ar Hyperimmunoglobulin E Syndrome 49
Non-Skeletal Hyper-Ige Syndrome 24
Nonskeletal Hyper Ige Syndrome 71
Hies, Autosomal Recessive 53
Autosomal Recessive Hies 24

Characteristics:

Orphanet epidemiological data:

55
combined immunodeficiency due to dock8 deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
early death may occur due to infection
distinct disorder from autosomal dominant hyper ige syndrome


HPO:

31
hyper-ige recurrent infection syndrome, autosomal recessive:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 55  
Rare immunological diseases


Summaries for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

NIH Rare Diseases : 49 Autosomal recessive hyper IgE syndrome (AR-HIES) is a very rare primary immunodeficiency syndrome characterized by highly elevated blood levels of immunoglobulin E (IgE), recurrent staphylococcal skin abscesses, and recurrent pneumonia. The same features are also seen in the more frequent autosomal dominant HIES syndrome. AR-HIES accounts for only a small minority of HIES cases, with about 130 affected families reported so far.In contrast to AD-HIES, the AR variant is further characterized by extreme hypereosinophilia (increase in the eosinophil count in the bloodstream); susceptibility to viral infections such as Herpes simplex and Molluscum contagiosum; involvement of the central nervous system; T-cell defects; and a high death rate. The dental, skeletal, connective tissue, and facial features present in AD-HIES are absent in AR-HIES. AR-HIES is inherited in an autosomal recessive fashion and is caused by mutations in the DOCK8 gene. Last updated: 1/14/2014

MalaCards based summary : Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive, also known as hyperimmunoglobulin e recurrent infection syndrome, autosomal recessive, is related to immunodeficiency 35 and hematopoietic stem cell transplantation, and has symptoms including chronic otitis media, skin ulcer and asthma. An important gene associated with Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive is DOCK8 (Dedicator Of Cytokinesis 8). The drugs Cyclophosphamide and Fludarabine have been mentioned in the context of this disorder. Affiliated tissues include skin, t cells and b cells.

OMIM : 53 Autosomal dominant hyper-IgE recurrent infection syndrome (147060) is a primary immunodeficiency disorder characterized by recurrent Staphylococcus aureus skin abscesses, increased serum IgE, and abnormalities of the connective tissue, skeleton, and dentition (Buckley et al., 1972; Grimbacher et al., 1999). The autosomal recessive form shares hyper-IgE, eosinophilia, and recurrent Staphylococcal infections, but is distinguished from autosomal dominant HIES by the lack of connective tissue and skeletal involvement (Renner et al., 2004). See also TYK2 deficiency (611521), a clinically distinct disease entity that includes characteristic features of both autosomal recessive HIES and mendelian susceptibility to mycobacterial disease (MSMD; 209950) (Minegishi et al., 2006). (243700)

UniProtKB/Swiss-Prot : 71 Hyperimmunoglobulin E recurrent infection syndrome, autosomal recessive: A rare disorder characterized by immunodeficiency, recurrent infections, eczema, increased serum IgE, eosinophilia and lack of connective tissue and skeletal involvement.

Genetics Home Reference : 24 Autosomal recessive hyper-IgE syndrome (AR-HIES) is a disorder of the immune system. A hallmark feature of the condition is recurrent infections that are severe and can be life-threatening. Skin infections can be caused by bacteria, viruses, or fungi. These infections cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling. People with AR-HIES also tend to have frequent bouts of pneumonia and other respiratory tract infections.

Related Diseases for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Diseases in the Hyper-Ige Recurrent Infection Syndrome, Autosomal Dominant family:

Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Diseases related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 immunodeficiency 35 11.4
2 hematopoietic stem cell transplantation 10.1
3 hyper ige syndrome 10.0

Symptoms & Phenotypes for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Symptoms via clinical synopsis from OMIM:

53
Respiratory Airways:
asthma

Laboratory Abnormalities:
eosinophilia
increased serum ige
decreased t cells
decreased b cells
decreased natural killer cells
more
Respiratory:
recurrent sinopulmonary infections

Neoplasia:
increased susceptibility to carcinomas, especially cancers related to cutaneous viral infections

Immunology:
recurrent bacterial infections
recurrent viral infections
recurrent fungal infections
impaired t cell immunity
impaired t cell proliferation and activation
more
Skin Nails Hair Skin:
atopic dermatitis
eczema, severe
skin abscesses, recurrent

Neurologic Central Nervous System:
increased neurologic sequelae of infections (rare)
hemiplegia (rare)
ischemic infarction (rare)
subarachnoid hemorrhage (rare)


Clinical features from OMIM:

243700

Human phenotypes related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

55 31 (show all 28)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 chronic otitis media 55 31 hallmark (90%) Very frequent (99-80%) HP:0000389
2 skin ulcer 55 31 hallmark (90%) Very frequent (99-80%) HP:0200042
3 asthma 55 31 hallmark (90%) Very frequent (99-80%) HP:0002099
4 recurrent viral infections 55 31 Very frequent (99-80%) HP:0004429
5 decrease in t cell count 55 31 hallmark (90%) Very frequent (99-80%) HP:0005403
6 b lymphocytopenia 55 31 hallmark (90%) Very frequent (99-80%) HP:0010976
7 pneumonia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002090
8 verrucae 55 31 hallmark (90%) Very frequent (99-80%) HP:0200043
9 squamous cell carcinoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0002860
10 recurrent bacterial skin infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0005406
11 onychomycosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0012203
12 atopic dermatitis 55 31 hallmark (90%) Very frequent (99-80%) HP:0001047
13 increased ige level 55 31 hallmark (90%) Very frequent (99-80%) HP:0003212
14 severe viral infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0005364
15 recurrent candida infections 55 31 hallmark (90%) Very frequent (99-80%) HP:0005401
16 recurrent sinusitis 55 31 hallmark (90%) Very frequent (99-80%) HP:0011108
17 anal canal squamous carcinoma 55 31 occasional (7.5%) Occasional (29-5%) HP:0006763
18 squamous cell carcinoma of the vulva 55 31 occasional (7.5%) Occasional (29-5%) HP:0030417
19 hemiplegia 31 HP:0002301
20 recurrent respiratory infections 55 Very frequent (99-80%)
21 neoplasm 31 HP:0002664
22 eczema 31 HP:0000964
23 subarachnoid hemorrhage 31 HP:0002138
24 recurrent bacterial infections 31 HP:0002718
25 recurrent fungal infections 31 HP:0002841
26 eosinophilia 31 HP:0001880
27 recurrent sinopulmonary infections 31 HP:0005425
28 cerebral vasculitis 31 HP:0005318

Drugs & Therapeutics for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Drugs for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 9)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cyclophosphamide Approved, Investigational Phase 2 50-18-0, 6055-19-2 2907
2
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
3
Busulfan Approved, Investigational Phase 2 55-98-1 2478
4
Lenograstim Approved, Investigational Phase 2 135968-09-1
5 Alkylating Agents Phase 2
6 Anesthetics Phase 2
7 Immunosuppressive Agents Phase 2
8 Antirheumatic Agents Phase 2
9 Yellow Dock Nutraceutical Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Pilot Study of Reduced-Intensity Hematopoietic Stem Cell Transplant of DOCK8 Deficiency Recruiting NCT01176006 Phase 2 Fludarabine(Fludara, Berlex Laboratories);Cyclophosphamide(CTX, Cytoxan);Busulfan (Busulfex)
2 Apheresis of Patients With Immunodeficiency Recruiting NCT01212055
3 Study of Clinical Features and Genetics of Hyperimmunoglobulin E Recurrent Infection Recruiting NCT00006150
4 Study of Voicing My CHOiCES as a Tool for Advanced Care Planning in Young Adults With Cancer Recruiting NCT02108028

Search NIH Clinical Center for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Genetic Tests for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Genetic tests related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

# Genetic test Affiliating Genes
1 Hyperimmunoglobulin E Recurrent Infection Syndrome, Autosomal Recessive 28 DOCK8

Anatomical Context for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

MalaCards organs/tissues related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

38
Skin, T Cells, B Cells

Publications for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Articles related to Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

# Title Authors Year
1
Genetic, clinical, and laboratory markers for DOCK8 immunodeficiency syndrome. ( 21178272 )
2010

Variations for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

UniProtKB/Swiss-Prot genetic disease variations for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

71
# Symbol AA change Variation ID SNP ID
1 DOCK8 p.Lys473Arg VAR_063753 rs112321280

ClinVar genetic disease variations for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 DOCK8 NM_203447.3(DOCK8): c.3494delC (p.Thr1165Lysfs) deletion Pathogenic rs113944762 GRCh38 Chromosome 9, 407033: 407033
2 DOCK8 NM_203447.3(DOCK8): c.3504_3505insTGGCTGCT (p.Ala1169Trpfs) insertion Pathogenic rs886037645 GRCh38 Chromosome 9, 407043: 407044
3 DOCK8 NM_203447.3(DOCK8): c.1418A> G (p.Lys473Arg) single nucleotide variant Pathogenic rs112321280 GRCh37 Chromosome 9, 336714: 336714
4 DOCK8 NM_203447.3(DOCK8): c.1126-395_2971-2751del deletion Pathogenic GRCh37 Chromosome 9, 333830: 394034
5 DOCK8 NC_000009.12: g.311734_398139del86406 deletion Pathogenic GRCh37 Chromosome 9, 311734: 398139
6 DOCK8 NM_203447.3(DOCK8): c.6019dupT (p.Tyr2007Leufs) duplication Pathogenic rs869312169 GRCh37 Chromosome 9, 452068: 452068
7 DOCK8 NC_000009.11: g.204193_343954del139762 deletion Pathogenic GRCh37 Chromosome 9, 204193: 343954
8 DOCK8 NC_000009.12: g.(?_214957)_(215049_?)del deletion Pathogenic GRCh38 Chromosome 9, 214957: 215049
9 DOCK8 NC_000009.12: g.(?_286441)_(289601_?)del deletion Pathogenic GRCh38 Chromosome 9, 286441: 289601
10 DOCK8 NC_000009.12: g.(?_304561)_(464239_?)del deletion Pathogenic GRCh37 Chromosome 9, 304561: 464239

Expression for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Search GEO for disease gene expression data for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive.

Pathways for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

GO Terms for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

Sources for Hyper-Ige Recurrent Infection Syndrome, Autosomal Recessive

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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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