MCID: IMM106
MIFTS: 43

Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked

Categories: Genetic diseases, Rare diseases, Immune diseases, Gastrointestinal diseases, Endocrine diseases, Blood diseases

Aliases & Classifications for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

MalaCards integrated aliases for Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

Name: Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked 53 12 13
X-Linked Autoimmunity-Allergic Dysregulation Syndrome 53 12 23 49 24
Xlaad 53 12 23 49 24
Diarrhea, Polyendocrinopathy, Fatal Infection Syndrome, X-Linked 53 12 49 24
Ipex Syndrome 23 49 24 36
Ipex 53 12 55 71
Xpid 53 12 23 49
Diabetes Mellitus, Congenital Insulin-Dependent, with Fatal Secretory Diarrhea 53 12 24
Enteropathy, Autoimmune, with Hemolytic Anemia and Polyendocrinopathy 53 49 24
Insulin-Dependent Diabetes Mellitus Secretory Diarrhea Syndrome 24 28 69
Autoimmunity-Immunodeficiency Syndrome, X-Linked 53 12 24
Iddm-Secretory Diarrhea Syndrome 53 12 24
Dmsd 53 12 49
Immune Dysregulation-Polyendocrinopathy-Enteropathy-X-Linked Syndrome 12 55
Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-Linked 12 24
Polyendocrinopathy, Immune Dysfunction, and Diarrhea, X-Linked 53 24
Autoimmune Enteropathy Type 1 12 55
Immunodeficiency, Polyendocrinopathy, and Enteropathy, X-Linked, Formerly 53
Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome 24
Polyendocrinopathy, Immune Dysfunction, and Diarrhea, X-Linked; Xpid 53
X-Linked Syndrome of Polyendocrinopathy, Immune Dysfunction,diarrhea 23
Immunodeficiency Polyendocrinopathy, Enteropathy, X-Linked Syndrome 71
Immunodeficiency, Polyendocrinopathy,enteropathy X-Linked Syndrome 23
Immunodysregulation, Polyendocrinopathy and Enteropathy X-Linked 49
X-Linked Autoimmunity-Allergic Dysregulation Syndrome; Xlaad 53
Polyendocrinopathy, Immune Dysfunction and Diarrhea X-Linked 49
Autoimmunity-Immunodeficiency Syndrome X-Linked 49
X-Linked Autoimmunity-Immunodeficiency Syndrome 71
Iddm-Secretory Diarrhea Syndrome; Dmsd 53
Iddm Secretory Diarrhea Syndrome 49

Characteristics:

Orphanet epidemiological data:

55
immune dysregulation-polyendocrinopathy-enteropathy-x-linked syndrome
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

53
Miscellaneous:
variable severity
death usually occurs in infancy or childhood if untreated

Inheritance:
x-linked recessive


HPO:

31
immunodysregulation, polyendocrinopathy, and enteropathy, x-linked:
Onset and clinical course variable expressivity
Inheritance x-linked recessive inheritance


Classifications:



External Ids:

OMIM 53 304790
Disease Ontology 12 DOID:0090110
ICD10 32 E31.0
Orphanet 55 ORPHA37042
UMLS via Orphanet 70 C0342288
ICD10 via Orphanet 33 E31.0
KEGG 36 H01971
UMLS 69 C0342288

Summaries for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

NIH Rare Diseases : 49 Immunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a rare autoimmune disease. it affects only males and starts in the first six months of life. The symptoms of IPEX syndrome include severe diarrhea, diabetes, skin conditions (such as eczema, erythroderma, or psoriasis), and thyroid disease (thyroiditis). IPEX syndrome is caused by changes (mutations) of the FOXP3 gene, which is located on the X chromosome. There are several other diseases that are very similar to the IPEX syndrome, caused by mutations in other genes and that affect both males and females. Treatment of IPEX syndrome consists of medications that limit immune system function; a bone marrow transplantation is the only treatment that can cure the disease, but it may have several complications. Research is ongoing for new and safer treatments.   Last updated: 2/20/2016

MalaCards based summary : Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked, also known as x-linked autoimmunity-allergic dysregulation syndrome, is related to autoimmune enteropathy and alpha/beta t-cell lymphopenia with gamma/delta t-cell expansion, severe cytomegalovirus infection, and autoimmunity, and has symptoms including diarrhea, hypothyroidism and type i diabetes mellitus. An important gene associated with Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked is FOXP3 (Forkhead Box P3), and among its related pathways/superpathways are Th17 cell differentiation and Inflammatory bowel disease (IBD). The drugs alemtuzumab and Fludarabine have been mentioned in the context of this disorder. Affiliated tissues include skin, thyroid and bone.

Disease Ontology : 12 A hypersensitivity reaction type II disease characterized by onset in infancy of refractory diarrhea, endocrinopathies, type 1 diabetes mellitus, and dermatitis that has material basis in mutation in the FOXP3 gene on chromosome Xp11.

Genetics Home Reference : 24 Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome primarily affects males and is caused by problems with the immune system. The immune system normally protects the body from foreign invaders, such as bacteria and viruses, by recognizing and attacking these invaders and clearing them from the body. However, the immune system can malfunction and attack the body's own tissues and organs instead, which is known as autoimmunity. IPEX syndrome is characterized by the development of multiple autoimmune disorders in affected individuals. Although IPEX syndrome can affect many different areas of the body, autoimmune disorders involving the intestines, skin, and hormone-producing (endocrine) glands occur most often. IPEX syndrome can be life-threatening in early childhood.

OMIM : 53 IPEX is an X-linked recessive immunologic disorder characterized by onset in infancy of severe diarrhea due to enteropathy, type 1 diabetes mellitus, and dermatitis. Other features may include hypothyroidism, autoimmune hemolytic anemia, thrombocytopenia, lymphadenopathy, hepatitis, and nephritis. The disorder may be fatal before age 2 years if not aggressively treated. Long-term therapeutic options include immunosuppression and hematopoietic stem cell transplantation (review by d'Hennezel et al., 2012). (304790)

UniProtKB/Swiss-Prot : 71 Immunodeficiency polyendocrinopathy, enteropathy, X-linked syndrome: Characterized by neonatal onset insulin-dependent diabetes mellitus, infections, secretory diarrhea, thrombocytopenia, anemia and eczema. It is usually lethal in infancy.

GeneReviews: NBK1118

Related Diseases for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Graphical network of the top 20 diseases related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:



Diseases related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked

Symptoms & Phenotypes for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Symptoms via clinical synopsis from OMIM:

53
Endocrine Features:
hypothyroidism
insulin-dependent diabetes mellitus (type i)

Abdomen Gastroin testinal:
ileus
enteropathy
diarrhea, secretory
villous atrophy seen on biopsy
chronic inflammation

Immunology:
immune dysregulation
increased serum ige
variable autoimmune disorders
lymphadenopathy may occur
autoantibodies

Hematology:
thrombocytopenia
eosinophilia
hemolytic anemia, autoimmune

Skin Nails Hair Skin:
eczema
atopy


Clinical features from OMIM:

304790

Human phenotypes related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

31 (show all 11)
# Description HPO Frequency HPO Source Accession
1 diarrhea 31 HP:0002014
2 hypothyroidism 31 HP:0000821
3 type i diabetes mellitus 31 HP:0100651
4 thrombocytopenia 31 HP:0001873
5 ileus 31 HP:0002595
6 eczema 31 HP:0000964
7 lymphadenopathy 31 HP:0002716
8 eosinophilia 31 HP:0001880
9 autoimmune hemolytic anemia 31 HP:0001890
10 villous atrophy 31 HP:0011473
11 immune dysregulation 31 HP:0002958

UMLS symptoms related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:


diarrhea

Drugs & Therapeutics for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Drugs for Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 39)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
alemtuzumab Approved, Investigational Phase 2 216503-57-0
2
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
3
Hydroxyurea Approved Phase 2 127-07-1 3657
4
Melphalan Approved Phase 2 148-82-3 460612 4053
5 Thiotepa Approved, Investigational Phase 2 52-24-4 5453
6
Miconazole Approved, Investigational, Vet_approved Phase 2 22916-47-8 4189
7
Mycophenolate mofetil Approved, Investigational Phase 2 128794-94-5 5281078
8
Mycophenolic acid Approved Phase 2 24280-93-1 446541
9
Vidarabine Approved, Investigational Phase 2 24356-66-9 21704 32326
10
Busulfan Approved, Investigational Phase 2 55-98-1 2478
11
Methotrexate Approved Phase 2 1959-05-2, 59-05-2 126941
12
Tacrolimus Approved, Investigational Phase 2 104987-11-3 445643 439492
13
Folic Acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
14
leucovorin Approved, Nutraceutical Phase 2 58-05-9 143 6006
15
Treosulfan Investigational Phase 2 299-75-2 9296
16 Alkylating Agents Phase 2
17 Antimetabolites Phase 2
18 Antimetabolites, Antineoplastic Phase 2
19 Immunosuppressive Agents Phase 2
20 Nucleic Acid Synthesis Inhibitors Phase 2
21 Anti-Bacterial Agents Phase 2
22 Antibiotics, Antitubercular Phase 2
23 Antibodies Phase 2
24 Antibodies, Monoclonal Phase 2
25 Antifungal Agents Phase 2
26 Anti-Infective Agents Phase 2
27 Antirheumatic Agents Phase 2
28 Antitubercular Agents Phase 2
29 Antiviral Agents Phase 2
30 Calcineurin Inhibitors Phase 2
31 Cyclosporins Phase 2
32 Dermatologic Agents Phase 2
33 Immunoglobulins Phase 2
34 Vidarabine Phosphate Phase 2
35 Antilymphocyte Serum Phase 2
36 Folic Acid Antagonists Phase 2
37 Vitamin B Complex Phase 2
38 Folate Nutraceutical Phase 2
39 Vitamin B9 Nutraceutical Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Reduced Intensity Conditioning for Non-Malignant Disorders Undergoing UCBT, BMT or PBSCT Recruiting NCT01962415 Phase 2 Hydroxyurea;Alemtuzumab;Fludarabine;Melphalan;Thiotepa
2 Alemtuzumab, Fludarabine Phosphate, and Total-Body Irradiation Followed by a Donor Stem Cell Transplant in Treating Patients With Immunodeficiency or Other Nonmalignant Inherited Disorders Active, not recruiting NCT00553098 Phase 2 Cyclosporine;Fludarabine Phosphate;Mycophenolate Mofetil
3 Treosulfan and Fludarabine Phosphate Before Donor Stem Cell Transplant in Treating Patients With Nonmalignant Inherited Disorders Suspended NCT00919503 Phase 2 Cyclosporine;Fludarabine Phosphate;Methotrexate;Mycophenolate Mofetil;Tacrolimus;Treosulfan
4 Natural History of Intestinal Inflammation in People With Primary Immune Dysregulations Recruiting NCT03278912

Search NIH Clinical Center for Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked

Genetic Tests for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Genetic tests related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

# Genetic test Affiliating Genes
1 Insulin-Dependent Diabetes Mellitus Secretory Diarrhea Syndrome 28 FOXP3

Anatomical Context for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

MalaCards organs/tissues related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

38
Skin, Thyroid, Bone, Bone Marrow

Publications for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Articles related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

(show all 42)
# Title Authors Year
1
From IPEX syndrome to FOXP3 mutation: a lesson on immune dysregulation. ( 26918796 )
2016
2
Clinical and structural impact of mutations affecting the residue Phe367 of FOXP3 in patients with IPEX syndrome. ( 26748374 )
2016
3
Familial IPEX syndrome: Different glomerulopathy in two siblings. ( 25712815 )
2015
4
Long-term disease course in a patient with severe neonatal IPEX syndrome. ( 25977242 )
2015
5
Identification of a novel nonsense mutation in the FOXP3 gene in a fetus with hydrops-Expanding the phenotype of IPEX syndrome. ( 26395338 )
2015
6
A challenging undertaking: Stem cell transplantation for immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. ( 26559324 )
2015
7
Disease specificity of anti-tryptophan hydroxylase-1 and anti-AIE-75 autoantibodies in APECED and IPEX syndrome. ( 25463430 )
2015
8
Clinical Case of Immune Dysregulation, Polyendocrinopaty, Enteropathy, X-Linked (IPEX) Syndrome with Severe Immune Deficiency and Late Onset of Endocrinopathy and Enteropathy. ( 24982679 )
2014
9
Extremely Early Onset IPEX Syndrome Caused by a Novel Small Exonic Deletion in FOXP3. ( 25187107 )
2014
10
Selective expansion of donor-derived regulatory T cells after allogeneic bone marrow transplantation in a patient with IPEX syndrome. ( 24224516 )
2014
11
Langerhans cell histiocytosis in IPEX syndrome: Possible role for natural regulatory T cells? ( 24628744 )
2014
12
Differences in FOXP3 and CD127 expression in Treg-like cells in patients with IPEX syndrome. ( 24727448 )
2014
13
Autoantibodies to harmonin and villin are diagnostic markers in children with IPEX syndrome. ( 24250806 )
2013
14
IPEX syndrome with membrano-proliferative nephrotic syndrome. ( 23549728 )
2013
15
IPEX Syndrome, FOXP3 and Cancer. ( 25844400 )
2013
16
Intestinal dysfunction in APECED syndrome could mimic IPEX syndrome. ( 23287803 )
2013
17
The immunogenetics of immune dysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. ( 22581967 )
2012
18
Proteomics plus genomics approaches in primary immunodeficiency: the case of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. ( 22132891 )
2012
19
[Girl with IPEX syndrome with low expression of Foxp3]. ( 23291488 )
2012
20
Functional type 1 regulatory T cells develop regardless of FOXP3 mutations in patients with IPEX syndrome. ( 21400500 )
2011
21
A novel mutation and unusual clinical features in a patient with immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. ( 21979562 )
2011
22
Autoimmune hepatitis type 2 in a child with IPEX syndrome. ( 21629128 )
2011
23
The spectrum of autoantibodies in IPEX syndrome is broad and includes anti-mitochondrial autoantibodies. ( 20650610 )
2010
24
Reduced FOXP3 expression causes IPEX syndrome onset: An implication from an IPEX patient and his disease-free twin brother. ( 20709600 )
2010
25
Identification of new FOXP3 mutations and prenatal diagnosis of IPEX syndrome. ( 20842625 )
2010
26
Digestive histopathological presentation of IPEX syndrome. ( 18820676 )
2009
27
Selective engraftment of donor CD4+25high FOXP3-positive T cells in IPEX syndrome after nonmyeloablative hematopoietic stem cell transplantation. ( 19478054 )
2009
28
FOXP3 expression following bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. ( 19471859 )
2009
29
Severe gastritis in an insulin-dependent child with an IPEX syndrome. ( 19633572 )
2009
30
Cutaneous manifestations of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. ( 18795917 )
2009
31
FOXP3 forkhead domain mutation and regulatory T cells in the IPEX syndrome. ( 19846862 )
2009
32
Epstein Barr virus induced lymphoma in a child with IPEX syndrome. ( 17828748 )
2008
33
Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. ( 16990602 )
2007
34
A potential screening tool for IPEX syndrome. ( 17378693 )
2007
35
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: an unusual cause of proteinuria in infancy. ( 17629750 )
2007
36
Submyeloablative cord blood transplantation corrects clinical defects seen in IPEX syndrome. ( 17115064 )
2007
37
Norwegian scabies mimicking onychomycosis and scalp dermatitis in a child with IPEX syndrome. ( 17224384 )
2007
38
Severe food allergy as a variant of IPEX syndrome caused by a deletion in a noncoding region of the FOXP3 gene. ( 17484868 )
2007
39
Clinical and molecular findings in IPEX syndrome. ( 16371377 )
2006
40
Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. ( 12161590 )
2002
41
A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA-->AAUGAA) leads to the IPEX syndrome. ( 11685453 )
2001
42
IPEX Syndrome ( 20301297 )
1993

Variations for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

UniProtKB/Swiss-Prot genetic disease variations for Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

71
# Symbol AA change Variation ID SNP ID
1 FOXP3 p.Phe371Cys VAR_011331 rs122467169
2 FOXP3 p.Ala384Thr VAR_011332 rs122467170
3 FOXP3 p.Arg397Trp VAR_011333 rs28935477
4 FOXP3 p.Ile363Val VAR_023569
5 FOXP3 p.Leu242Pro VAR_078971
6 FOXP3 p.Phe324Leu VAR_078972 rs122467173
7 FOXP3 p.Pro339Ala VAR_078973 rs886044787
8 FOXP3 p.Arg347His VAR_078974
9 FOXP3 p.Phe373Ala VAR_078975 rs122467172
10 FOXP3 p.Phe374Cys VAR_078976

ClinVar genetic disease variations for Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked:

6 (show all 17)
# Gene Variation Type Significance SNP ID Assembly Location
1 FOXP3 NM_014009.3(FOXP3): c.1189C> T (p.Arg397Trp) single nucleotide variant Pathogenic rs28935477 GRCh37 Chromosome X, 49107902: 49107902
2 FOXP3 FOXP3, 20-BP DEL, 3-BP INS, NT1290 indel Pathogenic
3 FOXP3 NM_014009.3(FOXP3): c.1112T> G (p.Phe371Cys) single nucleotide variant Pathogenic rs122467169 GRCh37 Chromosome X, 49108159: 49108159
4 FOXP3 NM_014009.3(FOXP3): c.1150G> A (p.Ala384Thr) single nucleotide variant Pathogenic rs122467170 GRCh37 Chromosome X, 49107941: 49107941
5 FOXP3 FOXP3, 2-BP DEL, 1481CT deletion Pathogenic
6 FOXP3 FOXP3, IVS9DS, A-G, +4 single nucleotide variant Pathogenic
7 FOXP3 NM_014009.3(FOXP3): c.750_752delGGA (p.Glu251del) deletion Pathogenic rs122467171 GRCh37 Chromosome X, 49111954: 49111956
8 FOXP3 FOXP3, 1-BP DEL deletion Pathogenic
9 FOXP3 NM_014009.3(FOXP3): c.1117_1118delTTinsGC (p.Phe373Ala) indel Pathogenic rs122467172 GRCh37 Chromosome X, 49108153: 49108154
10 FOXP3 NM_014009.3(FOXP3): c.970T> C (p.Phe324Leu) single nucleotide variant Pathogenic rs122467173 GRCh37 Chromosome X, 49109661: 49109661
11 FOXP3 FOXP3, 543C-T single nucleotide variant Pathogenic
12 FOXP3 NM_014009.3(FOXP3): c.3G> A (p.Met1Ile) single nucleotide variant Pathogenic rs122467174 GRCh37 Chromosome X, 49114960: 49114960
13 FOXP3 NM_014009.3(FOXP3): c.1099T> C (p.Phe367Leu) single nucleotide variant Pathogenic rs122467175 GRCh37 Chromosome X, 49108172: 49108172
14 FOXP3 NM_014009.3(FOXP3): c.727delG (p.Glu243Serfs) deletion Pathogenic rs797045588 GRCh38 Chromosome X, 49255723: 49255723
15 FOXP3 NM_014009.3(FOXP3): c.434C> T (p.Ala145Val) single nucleotide variant Likely pathogenic rs782528935 GRCh38 Chromosome X, 49257447: 49257447
16 FOXP3 NM_014009.3(FOXP3): c.1015C> G (p.Pro339Ala) single nucleotide variant Likely pathogenic rs886044787 GRCh37 Chromosome X, 49109616: 49109616
17 FOXP3 NM_014009.3(FOXP3): c.1222G> A (p.Val408Met) single nucleotide variant Likely pathogenic GRCh37 Chromosome X, 49107869: 49107869

Expression for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Search GEO for disease gene expression data for Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked.

Pathways for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Pathways related to Immunodysregulation, Polyendocrinopathy, and Enteropathy, X-Linked according to KEGG:

36
# Name Kegg Source Accession
1 Th17 cell differentiation hsa04659
2 Inflammatory bowel disease (IBD) hsa05321

GO Terms for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

Sources for Immunodysregulation, Polyendocrinopathy, and Enteropathy,...

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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