T-B-NK+ severe combined immunodeficiency due to complete RAG1/2 deficiency
Synonyms: T-B-NK+ SCID due to complete RAG1/2 deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive
- Age of onset
- Infancy
- Status
- active
Severe combined immunodeficiency due to complete RAG1/2 deficiency is a rare, genetic T-B- severe combined immunodeficiency disorder due to null mutations in recombination activating gene (RAG) 1 and/or RAG2 resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, normal NK counts and low or absent serum immunoglobulins; some patients may have eosinophilia.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | T-B-NK+ severe combined immunodeficiency due to complete RAG1/2 deficiency | T-B-NK+ SCID due to complete RAG1/2 deficiency |
| fr | Déficit immunitaire combiné sévère T-B-NK+ par déficit complet en RAG1/2 | DICS T-B-NK+ par déficit complet en RAG1/2 · IDCS T-B-NK+ par déficit complet en RAG1/2 · Immunodéficience combinée sévère T-B-NK+ par déficit complet en RAG1/2 · SCID T-B-NK+ par déficit complet en RAG1/2 |
| de | Immundefekt, kombinierter schwerer, T-B-NK+, durch kompletten RAG1/2-Mangel | T-B-NK+ SCID durch komplette RAG1/2-Defizienz |
| es | Inmunodeficiencia combinada grave T-B-NK+ por deficiencia completa de RAG1/2 | SCID T-B-NK+ por deficiencia completa de RAG1/2 · IDCG T-B-NK+ por deficiencia completa de RAG1/2 |
| it | Immunodeficienza combinata grave T-B-NK+ da deficit completo di RAG1/2 | SCID T-B-NK+ da deficit completo di RAG1/2 |
| nl | T-B-NK+ ernstige gecombineerde immuundeficiëntie door volledige RAG1/2-deficiëntie | T-B-NK+ SCID door volledige RAG1/2-deficiëntie |
| pt | Imunodeficiência grave combinada por défice completo de RAG1/2 | |
| pl | Ciężki złożony Niedobór odporności z powodu całkowitego deficytu RAG1/2 | SCID z powodu całkowitego niedoboru RAG1/2 |
| cs | Těžká kombinovaná imunodeficience způsobená kompletním RAG1/2 deficitem | SCID způsobená kompletním RAG1/2 deficitem |
| uk | Тяжкий комбінований імунодефіцит, зумовлений повною недостатністю RAG1/2 | SCID через повну недостатність RAG1/2 |
| zh | 完全性RAG1/2基因缺乏所致严重联合免疫缺陷 | 完全性RAG1/2基因缺乏所致SCID |
| tr | Tam RAG1/2 eksikliğine bağlı ağır kombine immün yetmezlik | Tam RAG1/2 eksikliğine bağlı SCID |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 601457 | E | validated | |
| ICD-10 | D81.1 | NTBT | attributed | validated |
| MONDO | 0011086 | E | validated | |
| UMLS | C4707355 | E | validated | |
| GARD | 10339 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (1):
- ORPHA:720314T-B-NK+ severe combined immunodeficiency without microcephaly
rare genetic diseases; rare immunological diseases; rare transplant-related disorders
No children.
Genes
2 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| RAG1 | Disease-causing germline mutation(s) in | Assessed | HGNC:9831 | ENSG00000166349 | 179615 | 11p12 | recombination activating 1 | 8810255[PMID] |
| RAG2 | Disease-causing germline mutation(s) in | Assessed | HGNC:9832 | ENSG00000175097 | 179616 | 11p12 | recombination activating 2 | 8810255[PMID] |
Prevalence and incidence
1 record| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Point prevalence | 1-9 / 100 000 | 1 / 100 000 | Europe | Value and class | Validated | European Medicines Agency 2014[OTHER] |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
HPO phenotypes
29 annotations · validated 2019-10-23| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0010975 | Abnormal B cell count | |
| HP:0011839 | Abnormal T cell count | |
| HP:0002720 | Decreased circulating IgA level | |
| HP:0004315 | Decreased circulating IgG level | |
| HP:0004313 | Decreased circulating antibody level | |
| HP:0002850 | Decreased circulating total IgM | |
| Frequent (79-30%) | ||
| HP:0031381 | Decreased lymphocyte proliferation in response to mitogen | |
| HP:0045080 | Decreased proportion of CD3-positive T cells | |
| HP:0001508 | Failure to thrive | |
| HP:0001945 | Fever | |
| HP:0001888 | Lymphopenia | |
| HP:0004385 | Protracted diarrhea | |
| HP:0002718 | Recurrent bacterial infections | |
| HP:0002743 | Recurrent enteroviral infections | |
| HP:0002841 | Recurrent fungal infections | |
| HP:0200117 | Recurrent upper and lower respiratory tract infections | |
| HP:0004429 | Recurrent viral infections | |
| HP:0031402 | Reduced antigen-specific T cell proliferation | |
| Occasional (29-5%) | ||
| HP:0040089 | Abnormal natural killer cell count | |
| HP:0001890 | Autoimmune hemolytic anemia | |
| HP:0002960 | Autoimmunity | |
| HP:0002910 | Elevated circulating hepatic transaminase concentration | |
| HP:0002240 | Hepatomegaly | |
| HP:0001433 | Hepatosplenomegaly | |
| HP:0001880 | Increased total eosinophil count | |
| HP:0002840 | Lymphadenitis | |
| HP:0000980 | Pallor | |
| HP:0000988 | Skin rash | |
| HP:0001873 | Thrombocytopenia | |
Run the differential on the 6 obligate / very frequent terms
Annotation source: 11133745[PMID]_16276422[PMID]_19458910[PMID]_24481607[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/331206
- This record as JSON: /data/d/331206.json