X-linked agammaglobulinemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

X-linked agammaglobulinemia (XLA) is a condition that affects the immune system and occurs almost exclusively in males. It is part of a group of disorders called primary immunodeficiencies (or inborn errors of immunity), in which part of the immune system does not function as it should. People with XLA have very few B cells, which are specialized white blood cells that help protect the body against infection. B cells can mature into the cells that produce special proteins called antibodies or immunoglobulins. Antibodies attach to specific foreign particles and germs, marking them for destruction. Individuals with XLA are more susceptible to infections because their body makes very few antibodies.

Children with XLA are usually healthy for the first 1 or 2 months of life because they are protected by antibodies acquired before birth from their mother. After this time, the maternal antibodies are cleared from the body, and the affected child begins to develop recurrent infections. .cf0{font-style:italic;font-family:Segoe UI;font-size:9pt;}Children with XLA generally take longer to recover from infections, and infections often occur again, even in children who are taking antibiotic medications.

The most common bacterial infections that occur in people with XLA are lung infections (pneumonia and bronchitis), ear infections (otitis), pink eye (conjunctivitis), and sinus infections (sinusitis). Infections that cause chronic diarrhea are also common. Recurrent infections can lead to organ damage. .cf0{font-style:italic;font-family:Segoe UI;font-size:9pt;}Treatments that replace antibodies can help prevent infections, improving the quality of life for people with XLA.

ORPHANET DEFINITION A clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, characterized in affected males by recurrent bacterial infections during infancy.

Inheritance

From: MedlinePlus Genetics, National Library of Medicine

X-linked recessive

Frequency in the source

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: 1-9 / 1 000 000; Worldwide; Value and class. Point prevalence: 1-9 / 1 000 000; France; Value and class. Point prevalence: 1-9 / 1 000 000; Italy; Value and class. Point prevalence: <1 / 1 000 000; United Kingdom; Value and class.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormality of the lymphatic system · Very frequent (99-80%)

An anomaly of the lymphatic system, a network of lymphatic vessels that carry a clear fluid called lymph unidirectionally towards either the right lymphatic duct or the thoracic duct, which in turn drain into the right and left subclavian veins respectively.

Abnormality of the tonsils · Very frequent (99-80%)

An abnormality of the tonsils.

Agammaglobulinemia · Very frequent (99-80%)

A lasting absence of total IgG and total IgA and total IgM in the blood circulation, whereby at most trace quantities can be measured.

Chronic diarrhea · Very frequent (99-80%)

The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks.

Chronic otitis media · Very frequent (99-80%)

Chronic otitis media refers to fluid, swelling, or infection of the middle ear that does not heal and may cause permanent damage to the ear.

Conjunctivitis · Very frequent (99-80%)

Inflammation of the conjunctiva.

Failure to thrive · Very frequent (99-80%)

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Fatigue · Very frequent (99-80%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Fever · Very frequent (99-80%)

Body temperature elevated above the normal range.

Glossoptosis · Very frequent (99-80%)

Posterior displacement of the tongue into the pharynx, i.e., a tongue that is mislocalised posteriorly.

Immunodeficiency · Very frequent (99-80%)

Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.

Recurrent cutaneous abscess formation · Very frequent (99-80%)

An increased susceptibility to cutaneous abscess formation, as manifested by a medical history of recurrent cutaneous abscesses.

Recurrent pneumonia · Very frequent (99-80%)

An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.

Short stature · Very frequent (99-80%)

A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).

Other findings in the same source

From: Orphanet

Additional reported features include Sinusitis (Very frequent (99-80%)); Skin rash (Very frequent (99-80%)); Skin ulcer (Very frequent (99-80%)); Abnormal lung morphology (Frequent (79-30%)); Arthritis (Frequent (79-30%)); Cellulitis (Frequent (79-30%)); Decreased total neutrophil count (Frequent (79-30%)); Hypocalcemia (Frequent (79-30%)); Meningitis (Frequent (79-30%)); Sensorineural hearing impairment (Frequent (79-30%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: MedlinePlus Genetics, National Library of Medicine

Childhood

Inheritance in the source

From: MedlinePlus Genetics, National Library of Medicine

X-linked recessive

Frequency and the population described

From: MedlinePlus Genetics, National Library of Medicine

Point prevalence: 1-9 / 1 000 000; Worldwide; Value and class. Point prevalence: 1-9 / 1 000 000; France; Value and class. Point prevalence: 1-9 / 1 000 000; Italy; Value and class. Point prevalence: <1 / 1 000 000; United Kingdom; Value and class.

Understanding the inheritance label

From: MedlinePlus Genetics

An X-linked recessive pattern involves a gene on the X chromosome. The number of X chromosomes and the particular genetic change influence how a condition is expressed. A genetic counsellor should interpret the result and the family history before discussing risks for relatives or future pregnancies.

Which doctor should you see?

The suggested department for discussing X-linked agammaglobulinemia is Allergy and Immunology, with a allergist / clinical immunologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the history suggest an allergy, an immune problem or another explanation?
• How would any proposed allergy or immune test change care?
• Is an individual emergency plan needed, and who should understand it?

Treatment discussions and follow-up

Where the source describes treatments, these are an overview of possible care, not a prescription for an individual. Ask which option applies to the confirmed diagnosis, what benefit is expected, what adverse effects to watch for and how progress will be assessed. Availability, approvals and local practice can differ from the country described in the source.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.