IEHDCM
MCID: INF158
MIFTS: 30

Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations (IEHDCM)

Categories: Blood diseases, Cardiovascular diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

MalaCards integrated aliases for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

Name: Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations 57 29 6 39 70
Infections, Recurrent, Associated with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations 6
Infections, Recurrent, Associated with Encephalopathy, Hepatic Dysfunction and Cardiovascular Malformations 72
Fadd-Related Immunodeficiency 58
Fadd Deficiency 57
Iehdcm 72

Characteristics:

Orphanet epidemiological data:

58
fadd-related immunodeficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
infections, recurrent, with encephalopathy, hepatic dysfunction, and cardiovascular malformations:
Inheritance autosomal recessive inheritance
Onset and clinical course death in childhood


Classifications:

Orphanet: 58  
Rare immunological diseases


Summaries for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

UniProtKB/Swiss-Prot : 72 Infections, recurrent, associated with encephalopathy, hepatic dysfunction and cardiovascular malformations: A condition with biological features of autoimmune lymphoproliferative syndrome such as high-circulating CD4(-)CD8(-)TCR-alpha-beta(+) T-cell counts, and elevated IL10 and FASL levels. Affected individuals suffer from recurrent, stereotypical episodes of fever, encephalopathy, and mild liver dysfunction sometimes accompanied by generalized seizures. The episodes can be triggered by varicella zoster virus (VZV), measles mumps rubella (MMR) attenuated vaccine, parainfluenza virus, and Epstein-Barr virus (EBV).

MalaCards based summary : Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations, also known as infections, recurrent, associated with encephalopathy, hepatic dysfunction, and cardiovascular malformations, is related to autoimmune lymphoproliferative syndrome and lymphoproliferative syndrome, and has symptoms including seizures An important gene associated with Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations is FADD (Fas Associated Via Death Domain). Affiliated tissues include liver, t cells and bone marrow, and related phenotypes are encephalopathy and decreased liver function

More information from OMIM: 613759

Related Diseases for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

Diseases related to Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 autoimmune lymphoproliferative syndrome 9.9
2 lymphoproliferative syndrome 9.9
3 bacterial infectious disease 9.9

Symptoms & Phenotypes for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

Human phenotypes related to Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

58 31 (show all 16)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 encephalopathy 58 31 very rare (1%) Obligate (100%) HP:0001298
2 decreased liver function 58 31 obligate (100%) Obligate (100%) HP:0001410
3 seizure 31 very rare (1%) HP:0001250
4 hepatic fibrosis 58 31 frequent (33%) Frequent (79-30%) HP:0001395
5 cerebral atrophy 58 31 very rare (1%) Frequent (79-30%) HP:0002059
6 ventricular septal defect 58 31 very rare (1%) Occasional (29-5%) HP:0001629
7 pulmonary artery atresia 58 31 very rare (1%) Occasional (29-5%) HP:0004935
8 autoimmune antibody positivity 58 31 occasional (7.5%) Occasional (29-5%) HP:0030057
9 howell-jolly bodies 31 very rare (1%) HP:0032550
10 hepatic bridging fibrosis 31 very rare (1%) HP:0012852
11 elevated serum alanine aminotransferase 31 very rare (1%) HP:0031964
12 left superior vena cava draining directly to the left atrium 31 very rare (1%) HP:0011669
13 portal inflammation 31 very rare (1%) HP:0033196
14 increased circulating interleukin 10 31 very rare (1%) HP:0033199
15 seizures 58 Obligate (100%)
16 recurrent infections 31 HP:0002719

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
encephalopathy
cerebral atrophy

Immunology:
recurrent infections
increased number of cd4(-)cd8(-)tcr-alpha-beta(+) t cells

Laboratory Abnormalities:
increased interleukin 10
increased fas ligand

Abdomen Spleen:
functional hyposplenism
howell-jolly bodies present

Cardiovascular Heart:
ventricular septal defect

Cardiovascular Vascular:
pulmonary atresia
superior vena cava left-sided, draining into left atrium

Abdomen Liver:
liver dysfunction, mild
transaminases mildly elevated

Clinical features from OMIM®:

613759 (Updated 05-Apr-2021)

UMLS symptoms related to Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:


seizures

Drugs & Therapeutics for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

Search Clinical Trials , NIH Clinical Center for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations

Genetic Tests for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

Genetic tests related to Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

# Genetic test Affiliating Genes
1 Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations 29 FADD

Anatomical Context for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

MalaCards organs/tissues related to Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

40
Liver, T Cells, Bone Marrow, Breast, B Cells

Publications for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

Articles related to Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

(show all 27)
# Title Authors PMID Year
1
Whole-exome-sequencing-based discovery of human FADD deficiency. 57 6 61
21109225 2010
2
FADD and Caspase-8 Regulate Gut Homeostasis and Inflammation by Controlling MLKL- and GSDMD-Mediated Death of Intestinal Epithelial Cells. 61
32362323 2020
3
Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation. 61
32296175 2020
4
Redundant and receptor-specific activities of TRADD, RIPK1 and FADD in death receptor signaling. 61
30741924 2019
5
Soluble TNF-like weak inducer of apoptosis (TWEAK) enhances poly(I:C)-induced RIPK1-mediated necroptosis. 61
30349023 2018
6
FADD is a key regulator of lipid metabolism. 61
27357657 2016
7
Fas-associated protein with death domain (FADD) regulates autophagy through promoting the expression of Ras homolog enriched in brain (Rheb) in human breast adenocarcinoma cells. 61
27013580 2016
8
The novel proteasome inhibitor carfilzomib activates and enhances extrinsic apoptosis involving stabilization of death receptor 5. 61
26009898 2015
9
fadD deletion and fadL overexpression in Escherichia coli increase hydroxy long-chain fatty acid productivity. 61
25117545 2014
10
RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. 61
25132550 2014
11
FADD is essential for glucose uptake and survival of thymocytes. 61
25078620 2014
12
FADD regulates thymocyte development at the β-selection checkpoint by modulating Notch signaling. 61
24901044 2014
13
Functional specific roles of FADD: comparative proteomic analyses from knockout cell lines. 61
23689606 2013
14
The adaptor protein FADD and the initiator caspase-8 mediate activation of NF-κB by TRAIL. 61
23096115 2012
15
Regulation of protein kinase C inactivation by Fas-associated protein with death domain. 61
22582393 2012
16
Midazolam activates the intrinsic pathway of apoptosis independent of benzodiazepine and death receptor signaling. 61
21701267 2011
17
FADD deficiency impairs early hematopoiesis in the bone marrow. 61
21115735 2011
18
The death domain of FADD is essential for embryogenesis, lymphocyte development, and proliferation. 61
19203997 2009
19
2-Chloro-2'-deoxyadenosine-induced apoptosis in T leukemia cells is mediated via a caspase-3-dependent mitochondrial feedback amplification loop. 61
18497995 2008
20
FADD negatively regulates lipopolysaccharide signaling by impairing interleukin-1 receptor-associated kinase 1-MyD88 interaction. 61
17785432 2007
21
The Fas-associated death domain protein is required in apoptosis and TLR-induced proliferative responses in B cells. 61
16709845 2006
22
FADD deficiency sensitises Jurkat T cells to TNF-alpha-dependent necrosis during activation-induced cell death. 61
16289096 2005
23
Conditional Fas-associated death domain protein (FADD): GFP knockout mice reveal FADD is dispensable in thymic development but essential in peripheral T cell homeostasis. 61
16116191 2005
24
Structural requirements for signal-induced target binding of FADD determined by functional reconstitution of FADD deficiency. 61
16009710 2005
25
Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro. 61
15915027 2005
26
T cell-specific FADD-deficient mice: FADD is required for early T cell development. 61
11353862 2001
27
FADD null mouse embryonic fibroblasts undergo apoptosis after photosensitization with the silicon phthalocyanine Pc 4. 61
11361017 2001

Variations for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

ClinVar genetic disease variations for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

6 (show all 27)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FADD NM_003824.3(FADD):c.315T>G (p.Cys105Trp) SNV Pathogenic 30267 rs387906839 GRCh37: 11:70052267-70052267
GRCh38: 11:70206161-70206161
2 FADD NM_003824.3(FADD):c.313T>C (p.Cys105Arg) SNV Likely pathogenic 242496 rs369869993 GRCh37: 11:70052265-70052265
GRCh38: 11:70206159-70206159
3 FADD NM_003824.3(FADD):c.475G>A (p.Ala159Thr) SNV Uncertain significance 471686 rs1555063819 GRCh37: 11:70052427-70052427
GRCh38: 11:70206321-70206321
4 FADD NM_003824.3(FADD):c.439A>G (p.Ile147Val) SNV Uncertain significance 662236 rs140822085 GRCh37: 11:70052391-70052391
GRCh38: 11:70206285-70206285
5 FADD NM_003824.3(FADD):c.306C>G (p.Asn102Lys) SNV Uncertain significance 640000 rs775250989 GRCh37: 11:70052258-70052258
GRCh38: 11:70206152-70206152
6 FADD NM_003824.3(FADD):c.452C>T (p.Thr151Ile) SNV Uncertain significance 575179 rs150178083 GRCh37: 11:70052404-70052404
GRCh38: 11:70206298-70206298
7 FADD NM_003824.4(FADD):c.51C>G (p.Ser17Arg) SNV Uncertain significance 953850 GRCh37: 11:70049616-70049616
GRCh38: 11:70203510-70203510
8 FADD NM_003824.4(FADD):c.248A>G (p.Glu83Gly) SNV Uncertain significance 954644 GRCh37: 11:70049813-70049813
GRCh38: 11:70203707-70203707
9 FADD NM_003824.3(FADD):c.168G>T (p.Glu56Asp) SNV Uncertain significance 539062 rs777501231 GRCh37: 11:70049733-70049733
GRCh38: 11:70203627-70203627
10 FADD NM_003824.3(FADD):c.31G>A (p.Val11Met) SNV Uncertain significance 579410 rs753665798 GRCh37: 11:70049596-70049596
GRCh38: 11:70203490-70203490
11 FADD NM_003824.3(FADD):c.307G>A (p.Val103Ile) SNV Uncertain significance 659707 rs200845739 GRCh37: 11:70052259-70052259
GRCh38: 11:70206153-70206153
12 FADD NM_003824.4(FADD):c.378C>G (p.Ile126Met) SNV Uncertain significance 946037 GRCh37: 11:70052330-70052330
GRCh38: 11:70206224-70206224
13 FADD NM_003824.4(FADD):c.152A>G (p.Glu51Gly) SNV Uncertain significance 1007395 GRCh37: 11:70049717-70049717
GRCh38: 11:70203611-70203611
14 FADD NM_003824.4(FADD):c.466G>A (p.Ala156Thr) SNV Uncertain significance 1008211 GRCh37: 11:70052418-70052418
GRCh38: 11:70206312-70206312
15 FADD NM_003824.4(FADD):c.304A>C (p.Asn102His) SNV Uncertain significance 1009010 GRCh37: 11:70052256-70052256
GRCh38: 11:70206150-70206150
16 FADD NM_003824.4(FADD):c.397T>C (p.Tyr133His) SNV Uncertain significance 1009886 GRCh37: 11:70052349-70052349
GRCh38: 11:70206243-70206243
17 FADD NM_003824.4(FADD):c.324G>A (p.Val108=) SNV Uncertain significance 844072 GRCh37: 11:70052276-70052276
GRCh38: 11:70206170-70206170
18 FADD NM_003824.4(FADD):c.52A>C (p.Ser18Arg) SNV Uncertain significance 935209 GRCh37: 11:70049617-70049617
GRCh38: 11:70203511-70203511
19 FADD NM_003824.3(FADD):c.313T>C (p.Cys105Arg) SNV Uncertain significance 242496 rs369869993 GRCh37: 11:70052265-70052265
GRCh38: 11:70206159-70206159
20 FADD NM_003824.4(FADD):c.419G>A (p.Arg140His) SNV Uncertain significance 1027224 GRCh37: 11:70052371-70052371
GRCh38: 11:70206265-70206265
21 FADD NM_003824.4(FADD):c.551G>A (p.Arg184His) SNV Uncertain significance 1039740 GRCh37: 11:70052503-70052503
GRCh38: 11:70206397-70206397
22 FADD NM_003824.4(FADD):c.8C>G (p.Pro3Arg) SNV Uncertain significance 1047817 GRCh37: 11:70049573-70049573
GRCh38: 11:70203467-70203467
23 FADD NM_003824.4(FADD):c.111G>A (p.Glu37=) SNV Likely benign 742721 rs753468219 GRCh37: 11:70049676-70049676
GRCh38: 11:70203570-70203570
24 FADD NM_003824.4(FADD):c.186C>G (p.Leu62=) SNV Likely benign 779632 rs572559406 GRCh37: 11:70049751-70049751
GRCh38: 11:70203645-70203645
25 FADD NM_003824.4(FADD):c.616G>A (p.Glu206Lys) SNV Likely benign 779666 rs61740746 GRCh37: 11:70052568-70052568
GRCh38: 11:70206462-70206462
26 FADD NM_003824.3(FADD):c.93G>T (p.Val31=) SNV Benign 471687 rs41268213 GRCh37: 11:70049658-70049658
GRCh38: 11:70203552-70203552
27 FADD NM_003824.4(FADD):c.9G>T (p.Pro3=) SNV Benign 713705 rs201376917 GRCh37: 11:70049574-70049574
GRCh38: 11:70203468-70203468

UniProtKB/Swiss-Prot genetic disease variations for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations:

72
# Symbol AA change Variation ID SNP ID
1 FADD p.Cys105Trp VAR_065124 rs387906839

Expression for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

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Pathways for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

GO Terms for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

Sources for Infections, Recurrent, with Encephalopathy, Hepatic Dysfunction,...

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