Information on TIDTA
Basic details
Name: T-cell immunodeficiency with thymic aplasia | Acronym: TIDTA
Alt. names: Nezelof syndrome
Gene: FOXN1 | MOI: Autosomal recessive | Mechanism of action: Loss of Function
No. of cases in DB: 3 | First reported in: 2019
Last updated on: 2023-04-01 03:29:24 by Xiao P. Peng
Description
To date, thirteen patients from nine families have been described with this condition (PMID: 8911612, 10206641, 20864124, 20978268, 21507891, 25173801, 28636882, 30903456, 35064468). The predominant findings are nail dystrophy, varying degrees of alopecia, thymic aplasia, erythroderma and skin rashes, along with severe T-cell immunodeficiency and recurrent viral, fungal, and opportunistic infections either disseminated or largely involving the sinopulmonary and GI tracts. Some patients also have chronic diarrhea, hepatosplenomegaly and/or lymphadenopathy, structural neurological abnormalities, developmental delays, and failure to thrive. Typically seen laboratory abnormalities include significantly skewed predominance of CD45RO+ memory over CD45RA+ naïve T cell populations and abnormal lymphocyte proliferative responses to mitogen or antigen stimulation, as well as hypogammaglobulinemia, increased IgE levels, eosinophilia, cytopenias, and sometimes reduced B and NK cell counts.
Management
Thymus transplantation has been shown to be curative for this condition, leading to functional T- and B-cell reconstitution (PMID: 20978268). One subject developed autoimmunity after transplantation.
3 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
102962 |
F | 215058 |
1 | 0 | U.S.A. | North American | PMID:31566583 [P1(II.1)]; PMID:37419334 [P1] | |
| 102965 |
F | 215059 |
1 | 0 | U.S.A. | North American | PMID:31566583 [P2(II.1)]; PMID:37419334 [P2] | |
| 106090 |
M | 215946 |
0 | 0 | Definitive | Saudi Arabia | Saudi | PMID:33464451 [P11]; PMID:37419334 [P11(27)]; PMID:31151968 [Fam.1:II.2(Patient)] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical term | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | Reduced T cell count |
3 (99.9%) | 0 (0.0%) | 0 (0.0%) |
| 2 | Lymphopenia |
2 (66.7%) | 0 (0.0%) | 1 (33.3%) |
| 3 | Severe combined immunodeficiency |
2 (66.7%) | 0 (0.0%) | 1 (33.3%) |
| 4 | (unusual) Viral infection |
2 (66.7%) | 0 (0.0%) | 1 (33.3%) |
| 5 | Severe parainfluenza infection |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 6 | Hematopoietic stem cell transplantation |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 7 | Reduced NK cell number |
1 (33.3%) | 1 (33.3%) | 1 (33.3%) |
| 8 | Persistent fever |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 9 | B-cell lymphoma |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 10 | Neonatal sepsis |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 11 | Thrombocytopenia |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 12 | Lymphadenopathy |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 13 | Mucocutaneous candidiasis |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 14 | Failure to thrive in infancy |
1 (33.3%) | 1 (33.3%) | 1 (33.3%) |
| 15 | Reduced number of B cells |
1 (33.3%) | 2 (66.7%) | 0 (0.0%) |
| 16 | Abnormal lymphoproliferation |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 17 | Alopecia |
1 (33.3%) | 2 (66.7%) | 0 (0.0%) |
| 18 | (unusual) Epstein-Barr virus infection |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 19 | Thymus aplasia |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 20 | Non-Hodgkin lymphoma |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 21 | Nail dystrophy |
1 (33.3%) | 2 (66.7%) | 0 (0.0%) |
| 22 | Oral candidiasis |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 23 | Respiratory distress |
1 (33.3%) | 0 (0.0%) | 2 (66.7%) |
| 24 | Epicanthus |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 25 | (unusual) Respiratory tract infection |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 26 | Autoimmunity |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 27 | (Unusual) bacterial infection |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 28 | Lung disease |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 29 | Enteropathy |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 30 | Diarrhea |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 31 | Failure to thrive |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 32 | Pneumonia |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 33 | Erythroderma |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
| 34 | BCGosis |
0 (0.0%) | 1 (33.3%) | 2 (66.7%) |
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| Prednisolone | Absent (1) for B-cell lymphoma |
| Antibiotics | Absent (1) for Persistent fever |
| Anti-Inflammatory agents | Absent (1) for B-cell lymphoma |
| Cyclophosphamide | Absent (1) for B-cell lymphoma |
| Anti-neoplastic agents | Absent (1) for B-cell lymphoma |
| Hematopoietic stem cell transplantation | Unspecified (1) for unspecified |
| Ganciclovir | Unspecified (1) for (unusual) Epstein-Barr virus infection |
| Vincristine | Absent (1) for B-cell lymphoma |
| Antiviral agent | Unspecified (1) for (unusual) Epstein-Barr virus infection |