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# X-linked (Bruton) agammaglobulinaemia

An inherited immune disorder in boys who make almost no B cells or antibodies, so they get repeated bacterial infections after maternal antibodies fade.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Neck lymph nodes](https://durgical.com/en/anatomy/lymph-nodes-of-neck/)
- [Palatine tonsils](https://durgical.com/en/anatomy/palatine-tonsil/)
- [Maxillary sinus](https://durgical.com/en/anatomy/maxillary-sinus/)

## Why it happens

- [Mendelian inheritance: autosomal dominant, recessive and X-linked](https://durgical.com/en/general-pathology/mendelian-inheritance-autosomal-dominant-recessive-and-x-linked/)
- [Innate and adaptive immunity: overview](https://durgical.com/en/physiology/innate-and-adaptive-immunity-overview/)
- [Immunoglobulins (antibodies)](https://durgical.com/en/biochemistry/enzymes/immunoglobulins/)

## What it is

A primary humoral immunodeficiency caused by mutations in Bruton tyrosine kinase (BTK), which arrests B-cell development at the pre-B stage. Affected boys have almost no circulating B cells and very low levels of all immunoglobulin classes.

## Who gets it

Rare: about 1 in 200,000 live births, almost exclusively in males. Symptoms usually start between 6 and 12 months of age. In Latin America, registries of the Latin American Society for Immunodeficiencies show that many cases are diagnosed years after the first infections.

## Causes

- Mutations in the BTK gene on the X chromosome
- X-linked recessive: carrier mothers pass it to half of their sons
- About half of patients have no family history (new mutation)

## Risk factors

- Male sex
- Brothers or maternal male relatives with recurrent infections or early deaths from infection
- Mother known to be a carrier

## Pathophysiology

Without BTK, pre-B cells in the bone marrow cannot mature, so there are no mature B cells, no plasma cells and no antibodies. T-cell immunity is intact. Newborns are protected by maternal IgG that crossed the placenta; once it wanes after about six months, infections by encapsulated bacteria (pneumococcus, Haemophilus influenzae), enteroviruses and Giardia appear. Lymphoid tissues that depend on B cells (tonsils, lymph-node follicles) are tiny or absent.

## Symptoms and signs

- Recurrent bacterial otitis media, sinusitis and pneumonia from about 6 months of age
- Infections by encapsulated bacteria (Streptococcus pneumoniae, Haemophilus influenzae)
- Absent or very small tonsils and lymph nodes despite repeated infections
- Chronic diarrhoea and malabsorption, often from Giardia
- Failure to thrive
- Severe or chronic enteroviral infection (meningoencephalitis), and vaccine-associated polio with oral polio vaccine

## Red flags

- Boy with two or more serious bacterial infections (pneumonia, meningitis, sepsis) after 6 months of age
- Tonsils not visible on examination in a child with recurrent infections
- Progressive headache, developmental regression or seizures: chronic enteroviral meningoencephalitis
- Need for intravenous antibiotics to clear infections, or infections that do not respond to oral antibiotics

## Diagnosis

**Clinical**
Suspected in a boy with recurrent bacterial infections starting after the first months of life, a family history of affected maternal male relatives, and scant lymphoid tissue on examination.

**Tests**
Serum immunoglobulins show very low IgG, IgA and IgM (interpret with age-specific ranges); absent vaccine antibody responses. Flow cytometry shows CD19+ B cells below 2% with normal T cells. Confirmation by absent BTK protein or BTK gene sequencing; carrier testing of the mother.

**Imaging**
[Chest](https://durgical.com/en/anatomy/region/chest/) imaging or CT for pneumonia and bronchiectasis; sinus imaging when indicated. A lateral neck radiograph may show absent adenoid tissue.

## Differential diagnosis

- Transient hypogammaglobulinaemia of infancy (B cells present, recovers spontaneously)
- Common variable immunodeficiency (later onset, B cells usually present)
- Severe combined immunodeficiency (T-cell defect, opportunistic infections, earlier onset)
- Secondary antibody loss (nephrotic syndrome, protein-losing enteropathy, malnutrition)

## Goal of treatment

Replace the missing antibodies for life, prevent and treat infections early, and protect the lungs from bronchiectasis.

## Treatment

**Medical**
Lifelong immunoglobulin replacement, intravenous or subcutaneous, adjusted to trough IgG levels and infections.

**Medical**
Prompt antibiotics for each bacterial infection; prophylactic antibiotics in some patients with recurrent infections or bronchiectasis.

**Follow-up**
Regular lung function and chest imaging, IgG trough levels, growth and infection diary; avoid live vaccines (oral polio, among others) in the patient.

**Lifestyle**
Chest physiotherapy when bronchiectasis is present, hand hygiene, and genetic counselling for the family.

## Complications

- Bronchiectasis and chronic lung disease
- Chronic enteroviral meningoencephalitis
- Vaccine-associated paralytic polio
- Sepsis and bacterial meningitis
- Chronic diarrhoea and malnutrition

## Prognosis

With early diagnosis and regular immunoglobulin replacement, most patients reach adulthood with good quality of life. Outcome depends on preventing lung damage before diagnosis; chronic enteroviral infection carries a poor prognosis.

## Prevention

- Carrier testing and genetic counselling for mothers and female relatives
- Testing of at-risk newborn boys before live vaccines are given

## Test yourself

Think of the answer, then tap the question to see it.

## Which gene is mutated in Bruton agammaglobulinaemia, and at which stage does B-cell development stop?

BTK (Bruton tyrosine kinase); development arrests at the pre-B-cell stage in the bone marrow.

## Why do infections usually start after about 6 months of age?

Because maternal IgG transferred across the placenta protects the infant until it wanes.

## Which physical finding suggests XLA in a boy with recurrent infections?

Absent or very small tonsils and lymph nodes.

## Which laboratory pattern confirms the diagnosis?

Very low IgG, IgA and IgM with almost absent CD19+ B cells and normal T cells; confirmed by BTK testing.

## Which vaccine must be avoided in XLA?

Live vaccines, especially oral polio vaccine, which can cause vaccine-associated paralytic polio.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/x-linked-agammaglobulinaemia/)

## Related conditions

- [Acute otitis media](https://durgical.com/en/conditions/acute-otitis-media/)
- [Acute rhinosinusitis](https://durgical.com/en/conditions/acute-rhinosinusitis/)
- [Community-acquired pneumonia](https://durgical.com/en/conditions/community-acquired-pneumonia/)
- [Bronchiectasis](https://durgical.com/en/conditions/bronchiectasis/)
- [Giardiasis](https://durgical.com/en/conditions/giardiasis/)
- [Bacterial meningitis](https://durgical.com/en/conditions/bacterial-meningitis/)
- [Adenosine deaminase deficiency (ADA-SCID)](https://durgical.com/en/conditions/adenosine-deaminase-deficiency/)
- [DiGeorge syndrome (22q11.2 deletion syndrome)](https://durgical.com/en/conditions/digeorge-syndrome/)
- [Wiskott–Aldrich syndrome](https://durgical.com/en/conditions/wiskott-aldrich-syndrome/)
- [Chronic granulomatous disease](https://durgical.com/en/conditions/chronic-granulomatous-disease/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [X-linked agammaglobulinemia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/x-linked-agammaglobulinemia/) (MedlinePlus, US National Library of Medicine, 2026); [About Primary Immunodeficiency (PI)](https://www.cdc.gov/primary-immunodeficiency/about/index.html) (Centers for Disease Control and Prevention (CDC), 2026).

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Source: https://durgical.com/en/conditions/x-linked-agammaglobulinaemia/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/x-linked-agammaglobulinaemia/