T-B+NK+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta deficiency

What it is

From: Orphanet

A rare T-B+ severe combined immunodeficiency characterized by a T cell-negative, B cell-positive, natural killer (NK) cell-positive immune phenotype. Patients present in infancy or early childhood with recurrent infections. Clinical manifestations may vary in severity depending on the underlying molecular defect, resulting in early death without bone marrow transplantation in some patients.

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.

Recurrent infections · Very frequent (99-80%)

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

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

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

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

Undetectable serum immunoglobulin A level at a value < 5 mg/dL (0.05 g/L).

Decreased lymphocyte proliferation in response to mitogen · Frequent (79-30%)

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.

Failure to thrive secondary to recurrent infections · Frequent (79-30%)

Insufficient weight gain or inappropriate weight loss for a child, that is attributed to an endogenous recurrent infections.

Fever · Frequent (79-30%)

Body temperature elevated above the normal range.

Lymphopenia · Frequent (79-30%)

A reduced number of lymphocytes in the blood.

Decreased proportion of CD3-positive T cells · Frequent (79-30%)

Anorexia · Occasional (29-5%)

Lack of desire to eat (loss of appetite).

Chronic oral candidiasis · Occasional (29-5%)

Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.

Diarrhea · Occasional (29-5%)

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

Erythroderma · Occasional (29-5%)

An inflammatory exfoliative dermatosis involving nearly all of the surface of the skin. Erythroderma develops suddenly. A patchy erythema may generalize and spread to affect most of the skin. Scaling may appear in 2-6 days and be accompanied by hot, red, dry skin, malaise, and fever.

Hepatitis · Occasional (29-5%)

Inflammation of the liver.

Hepatosplenomegaly · Occasional (29-5%)

Simultaneous enlargement of the liver and spleen.

Other findings in the same source

From: Orphanet

Additional reported features include Increased circulating immunoglobulin concentration (Occasional (29-5%)); Increased total eosinophil count (Occasional (29-5%)); Otitis media (Occasional (29-5%)); Pneumonia (Occasional (29-5%)); Recurrent abscess formation (Occasional (29-5%)); Recurrent candida infections (Occasional (29-5%)); Recurrent herpes (Occasional (29-5%)); Recurrent pneumonia (Occasional (29-5%)); Protracted diarrhea (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy

Inheritance in the source

From: Orphanet

Autosomal recessive

Frequency and the population described

From: Orphanet

Prevalence at birth: Unknown; Worldwide; Class only. Point prevalence: Unknown; Worldwide; Class only.

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-B+NK+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta 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 T-B+NK+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta 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.