Who can have DADA2?

DADA2 is usually inherited and often starts in early childhood.

It follows an autosomal recessive pattern, which means:

• A child needs two changed disease causing copies (variants) of the ADA2 gene (one from each parent) to develop DADA2
• Parents who carry one changed gene are called carriers
• If both parents are carriers:

Each child has a 25% chance of having DADA2

A 50% chance of being a carrier

A 25% chance of not having the gene change

Sometimes, DADA2 can occur without a family history due to a new (de novo) genetic change.

Genetic testing and family planning (AU/NZ context)

Family members may choose to have genetic testing, especially when planning children.

In Australia and New Zealand:

• Genetic counselling is available through public hospitals and specialist services
• Your GP or specialist can refer you
• Testing may be covered under public health systems (Medicare in Australia, public funding in NZ), depending on eligibility

What are the symptoms?

Symptoms can vary from person to person but often include:

Common symptoms

• Recurrent fevers
• Skin rash, often mottled or lace-like (livedo racemosa)
• Fatigue or feeling unwell
• Blood vessel and neurological symptoms
• Vasculitis
• Early-onset strokes (including in children)
• Blood and immune system problems
• Low white blood cells (especially B cells)
• Low antibodies (IgG, IgM)
• Frequent infections
• Anaemia
• Bone marrow failure
• Other features
• Enlarged liver and spleen
• Increased risk of blood cancers (rare but serious)
• Symptoms may come and go. These are often called:
• Flares (when symptoms worsen)
• Remission (when symptoms improve)

Triggers may include:

• Infections
• Stress
• Sometimes there is no clear trigger

What causes DADA2?

DADA2 is caused by changes (variants) in the ADA2 gene.

Genes provide instructions for making proteins. The ADA2 gene tells the body how to make the ADA2 enzyme, which helps control inflammation.

When the enzyme does not work properly:

• Inflammation is not controlled
• Blood vessels become damaged

How is DADA2 diagnosed?

Diagnosis can be difficult and may take time.

Doctors may:

• Review symptoms and medical history
• Rule out similar conditions (such as polyarteritis nodosa)

Tests may include:

• Blood tests showing:
• High inflammation markers (CRP, ESR)
• Low immune cells or antibodies
• Genetic testing to confirm changes in the ADA2 gene
• Enzyme activity testing if genetic results are unclear
• Early diagnosis is important to reduce the risk of serious complications such as stroke or organ damage.

What treatments are available?

Treatment depends on symptoms and severity.

Common treatments

1. Biologic medicines (main treatment)

Target a protein called TNF-alpha

Examples include:

• Adalimumab
• Infliximab
• Golimumab

These help:

• Control inflammation
• Reduce risk of stroke

2. Other medicines

• Corticosteroids or other immune-suppressing drugs may be used short-term
• These are not ideal long-term treatments

3. Immune support

Some people need immunoglobulin (IVIG) for low antibodies

4. Bone marrow transplant

May be needed in severe cases, especially with bone marrow failure

Access in Australia and New Zealand

Many biologic medicines are subsidised through:

• PBS (Pharmaceutical Benefits Scheme) in Australia
• Pharmac in New Zealand
• Access usually requires specialist approval

DADA2 can be serious and sometimes life-threatening.

People may experience:

• Risk of stroke and infections
• Ongoing fatigue and reduced energy
• Social isolation due to illness or infection risk

Managing DADA2 often involves a team of medical practitioners, such as:

• GP (family doctor)
• Paediatrician (for children)
• Rheumatologist
• Haematologist
• Neurologist
• Mental health and support