Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency

What it is

From: Orphanet

A rare, primary immunodeficiency characterized by variable combination of enteropathy, hypogammaglobulinemia, recurrent respiratory infections, granulomatous lymphocytic interstitial lung disease, lymphocytic infiltration of non-lymphoid organs (intestine, lung, brain, bone marrow, kidney), autoimmune thrombocytopenia or neutropenia, autoimmune hemolytic anemia and lymphadenopathy.

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.

Decreased circulating antibody level · Very frequent (99-80%)

An abnormally decreased level of immunoglobulin in blood.

Atopic dermatitis · Frequent (79-30%)

Atopic dermatitis (AD) or atopic eczema is an itchy, inflammatory skin condition with a predilection for the skin flexures. It is characterized by poorly defined erythema with edema, vesicles, and weeping in the acute stage and skin thickening (lichenification) in the chronic stage.

Autoimmune hemolytic anemia · Frequent (79-30%)

An autoimmune form of hemolytic anemia.

Autoimmune thrombocytopenia · Frequent (79-30%)

The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.

Decreased circulating IgA level · Frequent (79-30%)

Decreased levels of immunoglobulin A (IgA).

Decreased circulating IgG level · Frequent (79-30%)

An abnormally decreased level of immunoglobulin G (IgG) in blood.

Decreased circulating total IgM · Frequent (79-30%)

An abnormally decreased level of immunoglobulin M (IgM) in blood.

Diarrhea · Frequent (79-30%)

Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.

Hepatomegaly · Frequent (79-30%)

Abnormally increased size of the liver.

Lymphadenopathy · Frequent (79-30%)

Enlargement (swelling) of a lymph node.

Pneumonia · Frequent (79-30%)

Inflammation of any part of the lung parenchyma.

Recurrent lower respiratory tract infections · Frequent (79-30%)

An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.

Recurrent upper respiratory tract infections · Frequent (79-30%)

An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).

Splenomegaly · Frequent (79-30%)

Abnormal increased size of the spleen.

Other findings in the same source

From: Orphanet

Additional reported features include Atrophic gastritis (Occasional (29-5%)); Bronchiectasis (Occasional (29-5%)); Crohn's disease (Occasional (29-5%)); Eczematoid dermatitis (Occasional (29-5%)); Growth delay (Occasional (29-5%)); Inflammation of the large intestine (Occasional (29-5%)); Lymphocytic infiltration of the colorectal mucosa (Occasional (29-5%)); Lymphoma (Occasional (29-5%)); Neutropenia in presence of anti-neutropil antibodies (Occasional (29-5%)); Psoriasiform dermatitis (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult; Childhood

Inheritance in the source

From: Orphanet

Autosomal dominant

Frequency and the population described

From: Orphanet

Reported case(s): 17.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal dominant pattern means that one altered copy of a relevant gene can be sufficient for the condition. Some affected people inherit the change; others have a new change without an affected parent. The precise finding, family history and condition determine what this means for relatives.

Which doctor should you see?

The suggested department for discussing Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency 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

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

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.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

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.