X-linked lymphoproliferative disease due to XIAP deficiency

What it is

From: Orphanet

A rare, genetic, primary immunodeficiency disorder characterized by an abnormal immune response to Epstein-Barr virus (EBV) infection, caused by hemizygous mutations in the X-linked XIAP gene, resulting in B cell lymphoproliferation and manifesting with various phenotypes which include EBV-driven hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, recurrent splenomegaly, hepatitis, colitis, and intestinal bowel disease with features of Crohn's disease. Additional manifestations include variable auto-inflammatory symptoms such as uveitis, arthritis, skin abscesses, erythema nodosum, and nephritis. Neurological involvement is rare and lymphoma is never observed. Laboratory findings include normal or increased activated T cells, low or normal iNKT cells, and normal or reduced memory B cells.

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.

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.

Crohn's disease · Frequent (79-30%)

A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.

Hepatitis · Frequent (79-30%)

Inflammation of the liver.

Pancytopenia · Frequent (79-30%)

An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets).

Recurrent fever · Frequent (79-30%)

Periodic (episodic or recurrent) bouts of fever.

Splenic hemophagocytosis · Frequent (79-30%)

Phagocytosis of erythrocytes, lymphocytes or other hematopoietic precursors by histiocytes or macrophages observed in the spleen.

Splenomegaly · Frequent (79-30%)

Abnormal increased size of the spleen.

Jejunoileal ulceration · Frequent (79-30%)

Arthritis · Occasional (29-5%)

Inflammation of a joint.

Cholangitis · Occasional (29-5%)

Inflammation of the biliary ductal system, affecting the intrahepatic or extrahepatic portions, or both.

Colitis · Occasional (29-5%)

Colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine (colon, cecum and rectum). Colitides may be acute and self-limited or chronic, and broadly fit into the category of digestive diseases.

Cutaneous abscess · Occasional (29-5%)

A circumscribed area of pus or necrotic debris in the skin (within the epidermis or dermis).

Decreased circulating antibody level · Occasional (29-5%)

An abnormally decreased level of immunoglobulin in blood.

Erythema nodosum · Occasional (29-5%)

An erythematous eruption commonly associated with drug reactions or infection and characterized by inflammatory nodules that are usually tender, multiple, and bilateral.

Other findings in the same source

From: Orphanet

Additional reported features include Inflammation of the large intestine (Occasional (29-5%)); Nephritis (Occasional (29-5%)); Recurrent infections (Occasional (29-5%)); Reduced natural killer cell count (Occasional (29-5%)); Renal insufficiency (Occasional (29-5%)); Severe Epstein Barr virus infection (Occasional (29-5%)); Uveitis (Occasional (29-5%)); Hepatic failure (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Adolescent; Adult; Childhood; Infancy

Inheritance in the source

From: Orphanet

X-linked recessive

Frequency and the population described

From: Orphanet

Reported case(s): 100.0; 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 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 lymphoproliferative disease due to XIAP deficiency 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 X-linked lymphoproliferative disease due to XIAP deficiency. 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.