Definition
PAX5 deficiency or a predisposition to ALL 3 (OMIM #615545) is a genetic disease caused by mutations in the PAX5 gene. Those suffering from it have an increased risk of developing B-ALL. Other hematological diseases or solid tumors have not been described to date.
Key Data
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| Synonym | Predisposition to ALL 3 |
| Gene | PAX5 |
| Gene product | PAX5 (paired box protein 5) |
| Function | Transcription factor that regulates the differentiation of B cells |
| Heredity | Autosomal dominant |
| Prevalence | Unknown |
| Genotype-phenotype correlation | Genotype-phenotype correlation The p.G183S missense mutation has so far been found in all known leukemia patients who are carriers of a PAX5 mutation. However, there is also proof that the missense mutation is present in phenotypically healthy people with a PAX5 mutation. There is reduced transcriptional activity which points to a partial loss-of-function. |
| Penetrance | Incomplete |
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Diagnosis
Clinical Diagnostics
The possibility of a PAX5 mutation should be considered and tested for genetically in families with multiple cases of acute lymphoblastic B-cell leukemia (B-ALL) and when a somatic 9p deletion has been genetically diagnosed as part of the ALL diagnosis.
Genetic Diagnostics
The diagnosis of “PAX5 deficiency” is confirmed by detection of a PAX5 germline mutation by single-gene analysis or the use of panel studies consisting of multiple genes.
Differential Diagnoses
B-ALL with another underlying mutation
Clinical Presentation
The only clinical manifestation of a PAX5 mutation described to date is acute lymphoblastic B-cell leukemia or pre-B-ALL. In all of the patients, the leukemia was diagnosed during childhood, which suggests that the risk of developing B-ALL greatly decreases after the first decade of life.
PAX5 deficiency exhibits incomplete penetrance, meaning that carriers of the PAX5 mutation may be phenotypically healthy – in other words, not suffering from B-ALL.
Other types of hematological neoplasia or solid tumors have not yet been observed in connection with PAX5 mutations.
Therapeutic Considerations
Treatment of B-ALL in patients with a PAX5 mutation should be discussed thoroughly with the corresponding study center.
When a stem cell transplant is planned with an HLA-compatible sibling as the donor, he or she should first undergo a PAX5 mutational analysis to rule out the possibility of being an asymptomatic carrier of the same genetic syndrome.
Surveillance Recommendations
Surveillance Recommendations
Since PAX5 deficiency is a very rare disease, there is not yet sufficient data to provide standardized surveillance recommendations.
As with other leukemia predisposition syndromes, the following examinations should be conducted on a regular basis:
Clinical examinations
Complete blood count once a year
Bone marrow puncture only with unstable blood values / clinically suspected leukemia
Additional Information
Open Clinical Trials / Registries
Support Groups
Unfortunately, we are as yet unaware of any existing support groups for patients with PAX5 deficiency. We will add new information as it becomes available.
