What is PAX5 deficiency?

PAX5 deficiency, or a predisposition to ALL 3, is a genetic disease caused by mutations – or genetic changes – in the PAX5 gene. Those suffering from it have an increased risk of developing acute lymphoblastic B-cell leukemia (B-ALL). Other diseases of the blood-formation system or tumors of other organs have not been described to date.

How is PAX5 deficiency diagnosed?

Suspected Diagnosis

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). There is also reason to suspect a PAX5 mutation if a 9p deletion has been detected during genetic diagnostics for ALL, whereby further genetic diagnostics should follow.

Genetic Diagnostics

The diagnosis of “PAX5 deficiency” is confirmed by detection of a mutation, i.e. a genetic alteration in the PAX5 gene.

What is the risk of cancer?

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 is significantly reduced after the first decade of life.

PAX5 deficiency exhibits incomplete penetrance, meaning that carriers of the PAX5 mutation may be healthy – in other words, they may not be affected by B-ALL. It is not yet known how high the probability is that a PAX5 mutation carrier will develop leukemia.

Other diseases of the blood-formation system or tumors affecting other organs have not to date been associated with PAX5 mutations.

What causes PAX5 deficiency?

Die PAX5-Defizienz beruht auf einer Mutation, also einer genetischen Veränderung des PAX5-Gens. Dieses Gen kodiert für den sogenannten Transkriptionsfaktor PAX5, der in der Entwicklung von B-Lymphozyten, eine bestimmte Gruppe weißer Blutkörperchen, eine wichtige Rolle spielt. Liegt nun das PAX5-Gen in einer veränderten Form vor, kann auch der Transkriptionsfaktor nicht mehr korrekt funktionieren und es kommt zur Entstehung von akuten Leukämien der B-Zelllinie.

Is there a treatment?

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 a sibling as the donor, he or she should first undergo a PAX5 mutation analysis to rule out the possibility of being an asymptomatic carrier of the same genetic syndrome.

Surveillance Recommendations for the Early Detection of Cancer

Surveillance Recommendations

Since PAX5 deficiency is a very rare disease, there is not yet sufficient data to provide standardized surveillance recommendations.

  • Clinical examinations

  • Complete blood count once a year

  • Bone marrow puncture only when blood values are unstable / leukemia is clinically suspected

Self-Care and Support

What should I pay special attention to?

You should consult a doctor as soon as you notice any increased or hard-to-stop bleeding (e.g. long-lasting or frequent nose bleeds), increased bruising, fatigue or that you feel sick, have a fever, night sweats, are pale, or suffer from frequent infections. In addition, you should go see a doctor right away if you have swollen lymph nodes or bone pain. If you develop new anomalies or complaints, they should likewise be evaluated as soon as possible.

Support Groups and Additional Information

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.