Information on IMD87

Name: Immunodeficiency 87 | Acronym: IMD87
Alt. names: DEF6 deficiency | Immunodeficiency 87 and autoimmunity

Gene: DEF6 | MOI: Autosomal recessive | Mechanism of action:

No. of cases in DB: 19 | First reported in: 2019

Last updated on: 2023-02-28 by Andrés Caballero-Oteyza

OMIM: 619573

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Description

Affected individuals usually present in infancy or early childhood with increased susceptibility to infections, often Epstein-Barr virus (EBV), as well as with enteropathy, lymphadenopathy or autoimmune manifestations, predominantly hemolytic anemia. Cardiomyopathy has also been described. Laboratory studies may show mild CD4 and CD8 lymphopenia and low or normal B cell numbers. The disorder results primarily from defects in T-reg function, which causes both immunodeficiency and overall immune dysregulation.

Management

Description of management option has not been reviewed yet.

Please mind that full curation of this condition has not been completed yet. It is currently ongoing.

Summary of clinical findings

[Considering only Definitive and Possible cases]

Rank Clinical phenotype Present Absent Unreported
1 Hepatopathyarrow icon 2 (28.6%) 0 (0.0%) 5 (71.4%)
2 Intrauterine growth retardationarrow icon 2 (28.6%) 0 (0.0%) 5 (71.4%)
3 Abnormal lymphoproliferationarrow icon 2 (28.6%) 1 (14.3%) 4 (57.1%)
4 Enteropathyarrow icon 2 (28.6%) 0 (0.0%) 5 (71.4%)
5 (unusual) Cytomegalovirus infectionarrow icon 2 (28.6%) 0 (0.0%) 5 (71.4%)
6 Hypertelorismarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
7 Villous atrophyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
8 Necrotizing enterocolitisarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
9 Hepatic steatosisarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
10 Thrombocytopeniaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
11 Biventricular hypertrophyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
12 Jaundicearrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
13 Septicaemiaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
14 Rectal ulcerarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
15 Feverarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
16 Cholestasisarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
17 Hepatosplenomegalyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
18 Oligohydramniosarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
19 Atrial septal defectarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
20 Dilated cardiomyopathyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
21 Complete atrioventricular canal defectarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
22 Elevated hepatic transaminasesarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
23 Premature rupture of membranesarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
24 Metabolic acidosisarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
25 Vomitingarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
26 Autoimmunityarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
27 Hypertriglyceridemiaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
28 Recurrent infectionsarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
29 Autoimmune hemolytic anemiaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
30 Abnormal blood ion concentrationarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
31 Autoimmune cytopeniaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
32 Nevusarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
33 Abnormality of the gastric mucosaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
34 Hepatomegalyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
35 Duodenitisarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
36 Pulmonary Hypertensionarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
37 Congestive heart failurearrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
38 Diarrheaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
39 Cardiomyopathyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
40 Hepatic failurearrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
41 Hypokalemiaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
42 Hypogammaglobulinemiaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
43 Postnatal growth retardationarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
44 Abnormal adipose tissue morphologyarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
45 Hemolytic anemiaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
46 Ascitesarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
47 Perianal rasharrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
48 Hypertensionarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
49 Respiratory distressarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
50 Anasarcaarrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
51 Cleft palatearrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
52 Anal fissurearrow icon 1 (14.3%) 0 (0.0%) 6 (85.7%)
53 Tendonitisarrow icon 0 (0.0%) 1 (14.3%) 6 (85.7%)
54 Lymphadenopathyarrow icon 0 (0.0%) 1 (14.3%) 6 (85.7%)
55 Hodgkin lymphomaarrow icon 0 (0.0%) 1 (14.3%) 6 (85.7%)
56 Henoch-Schönlein Purpuraarrow icon 0 (0.0%) 1 (14.3%) 6 (85.7%)
57 Synovitisarrow icon 0 (0.0%) 1 (14.3%) 6 (85.7%)
58 Arthritisarrow icon 0 (0.0%) 1 (14.3%) 6 (85.7%)
59 Persistent EBV viremiaarrow icon 0 (0.0%) 2 (28.6%) 5 (71.4%)
Age of onset
distribution

Please mind that full curation of this condition has not been completed yet. It is currently ongoing.

Summary of treatment outcomes

[Considering only Definitive and Possible cases]

Treatment ⓘ Responses & clinical indications
Immunosuppressive agents
 Excelent/Remision (2) for unspecified; Diarrhea. Mild (1) for Diarrhea. Moderate (1) for Autoimmune hemolytic anemia. Unspecified (1) for Diarrhea
Corticosteroids
[Immunosuppressive agents] [Anti-Inflammatory agents]
 Mild (1) for Diarrhea. Moderate (1) for Autoimmune hemolytic anemia. Excelent/Remision (1) for unspecified
Azathioprine
[Immunosuppressive agents]
 Moderate (1) for Autoimmune hemolytic anemia. Excelent/Remision (1) for unspecified
Prednisolone
[Corticosteroids]
 Mild (1) for Diarrhea
Biological agents
 Moderate (1) for Autoimmune hemolytic anemia
Monoclonal antibodies
[Biological agents]
 Moderate (1) for Autoimmune hemolytic anemia
Rituximab
[Monoclonal antibodies] [Anti-neoplastic agents]
 Moderate (1) for Autoimmune hemolytic anemia
Intravenous immunoglobulin therapy
 Unspecified (1) for Hypogammaglobulinemia
Cyclosporine
[Immunosuppressive agents]
 Unspecified (1) for Diarrhea
Blood transfusion
 Unspecified (1) for Autoimmune hemolytic anemia
Ursodeoxycholic Acid
 Excelent/Remision (1) for Elevated hepatic transaminases
Hematopoietic stem cell transplantation
 Unspecified (1) for unspecified
Ganciclovir
[Antiviral agent]
 Excelent/Remision (1) for unspecified
Abatacept
[Immunosuppressive agents]
 Excelent/Remision (1) for Diarrhea
Valganciclovir
[Antiviral agent]
 Excelent/Remision (1) for unspecified
Antiviral agent
 Excelent/Remision (1) for unspecified

Please mind that full curation of this condition has not been completed yet. It is currently ongoing.

19 reported cases added to GenIA

SubjectID Sex Fam.ID AD AFM Validity Country Population Reference & Pub.code
105339arrow icon F 215701tree icon 0 Pakistani PMID:31308374 [Fam.A:III.4(P1)]
105361arrow icon F 215701tree icon Pakistani PMID:31308374 [Fam.A:III.3(P2)]
105362arrow icon M 215721tree icon Iraqi PMID:31308374 [Fam.B:II.1(P3)]
105382arrow icon M 215733tree icon 16 France Moroccan PMID:32562707 [Fam.1:II.1(Pt 1)]
105389arrow icon F 215733tree icon 10 France Moroccan PMID:32562707 [Fam.1:II.2(Pt 2)]
105394arrow icon F 215733tree icon 12 France Moroccan PMID:32562707 [Fam.1:II.3(Pt 3)]
105396arrow icon F 215733tree icon 1 France Moroccan PMID:32562707 [Fam.1:II.4(Pt 4)]
105592arrow icon M 215701tree icon Pakistani PMID:31308374 [Fam.A:II.2(II-2)]
105593arrow icon F 215701tree icon Pakistani PMID:31308374 [Fam.A:II.3(II-3)]
105594arrow icon M 215701tree icon Pakistani PMID:31308374 [Fam.A:II.1(II-1)]
105595arrow icon F 215701tree icon Pakistani PMID:31308374 [Fam.A:III.1(III-1)]
105597arrow icon F 215701tree icon Pakistani PMID:31308374 [Fam.A:II.4(II-4)]
105598arrow icon M 215701tree icon Pakistani PMID:31308374 [Fam.A:II.5(II-5)]
105599arrow icon M 215701tree icon Pakistani PMID:31308374 [Fam.A:II.6(II-6)]
105600arrow icon F 215701tree icon Pakistani PMID:31308374 [Fam.A:II.7(II-7)]
105602arrow icon F 215701tree icon Pakistani PMID:31308374 [Fam.A:I.4(I-2)]
105610arrow icon U 215701tree icon Pakistani PMID:31308374 [Fam.A:III.5(III-5)]
105613arrow icon M 215721tree icon Iraqi PMID:31308374 [Fam.B:I.1(I.1)]
105614arrow icon F 215721tree icon Iraqi PMID:31308374 [Fam.B:I.2(I.2)]

AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).