T-cell immunodeficiency with thymic aplasia

What it is

From: Orphanet

A rare primary immunodeficiency with autosomal or X-linked recessive inheritance, characterized by thymic aplasia in the absence of other congenital abnormalities, with profound T-cell deficiency, while serum immunoglobulin levels are normal or increased. Patients present with chronic or recurrent infections in infancy including candidiasis, skin, pulmonary and urinary tract infections, chronic diarrhea, and failure to thrive.

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.

Aplasia of the thymus · Obligate (100%)

Absence of the thymus. This feature may be appreciated by the lack of a thymic shadow upon radiographic examination.

Cellular immunodeficiency · Very frequent (99-80%)

An immunodeficiency characterized by defective cell-mediated immunity or humoral immunity.

Decreased lymphocyte proliferation in response to mitogen · Very frequent (99-80%)

Abnormal decrease of T cell proliferation in response to mitogenic stimuli. This is commonly measured through intracellular expression of Ki67, decreasing surface expression of carboxyfluorescein diacetate (CFSE), or 3H-thymidine incorporation. Length of incubation, specific stimulus and strength of stimulation may vary between laboratories.

Decreased total T cell count · Very frequent (99-80%)

Abnormal decrease in the absolute number of T cells, commonly characterized as CD3+ lymphocytes, per microliter of blood, compared to a reference range for a given sex and age-group. These may include both TCR alpha/beta and gamma/delta T cells.

Recurrent infections · Very frequent (99-80%)

Increased susceptibility to infections as manifested by repeated bouts of infection.

Reduced proportion of naive T cells · Very frequent (99-80%)

An abnormally decreased proportion of naive T cells relative to the total number of T cells.

Severe T-cell immunodeficiency · Very frequent (99-80%)

A primary immune deficiency that is characterized by defects or deficiencies of T-lymphocytes that causes specific susceptibility to intracellular micro-organisms.

Autoimmunity · Frequent (79-30%)

The occurrence of an immune reaction against the organism's own cells or tissues.

Failure to thrive · Frequent (79-30%)

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

Opportunistic infection · Frequent (79-30%)

An infection that is caused by a pathogen that would generally not be able to cause an infection in a host with a normal immune system. Such pathogens take advantage of the opportunity, so to speak, that is provided by a weakened immune system.

Pneumonia · Frequent (79-30%)

Inflammation of any part of the lung parenchyma.

Recurrent bacterial infections · Frequent (79-30%)

Increased susceptibility to bacterial infections as manifested by recurrent episodes of bacterial infection.

Recurrent infection of the gastrointestinal tract · Frequent (79-30%)

Recurrent infection of the gastrointestinal tract.

Severe infection · Frequent (79-30%)

A type of infection that is regarded as a sign of a pathological susceptibility to infection because of unusual severity or intensity of the infection.

Other findings in the same source

From: Orphanet

Additional reported features include Severe viral infection (Frequent (79-30%)); Chronic oral candidiasis (Occasional (29-5%)); Chronic otitis media (Occasional (29-5%)); Combined immunodeficiency (Occasional (29-5%)); Coombs-positive hemolytic anemia (Occasional (29-5%)); Diarrhea (Occasional (29-5%)); Eczematoid dermatitis (Occasional (29-5%)); Hypocalcemic tetany (Occasional (29-5%)); Hypothyroidism (Occasional (29-5%)); Invasive fungal infection (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing T-cell immunodeficiency with thymic aplasia 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 T-cell immunodeficiency with thymic aplasia. 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.