T-B+NK- severe combined immunodeficiency due to JAK3 deficiency

What it is

From: Orphanet

Severe combined immunodeficiency (SCID) T-B+ due to JAK3 deficiency is a form of SCID characterized by severe and recurrent infections, associated with 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.

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.

Impaired lymphocyte transformation with phytohemagglutinin · Very frequent (99-80%)

Lack of T cell function · Very frequent (99-80%)

Absent natural killer cells · Frequent (79-30%)

Absence of detectable circulating NK cells, commonly characterized as CD3-CD19- and CD16+ or CD56+ lymphocytes, in the blood. Usually, less than 20 cells per microlitre is considered to be an absence.

Chronic diarrhea · Frequent (79-30%)

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

Chronic oral candidiasis · Frequent (79-30%)

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.

Lymphopenia · Frequent (79-30%)

A reduced number of lymphocytes in the blood.

Recurrent opportunistic infections · Frequent (79-30%)

Increased susceptibility to opportunistic infections as manifested by recurrent episodes of infection by opportunistic agents, i.e., by microorganisms that do not usually cause disease in a healthy host, but are able to infect a host with a compromised immune system.

Recurrent respiratory infections · Frequent (79-30%)

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

Acute otitis media · Occasional (29-5%)

Acute otitis media is a short and generally painful infection of the middle ear.

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

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

Decreased circulating total IgM · Occasional (29-5%)

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

Decreased total B cell count · Occasional (29-5%)

The absolute number of B cells in the blood, per microlitre is below the lower limit of normal of the reference range for the appropriate sex and age-group.

Other findings in the same source

From: Orphanet

Additional reported features include Pustule (Occasional (29-5%)); Recurrent infection of the gastrointestinal tract (Occasional (29-5%)); Recurrent pneumonia (Occasional (29-5%)); Recurrent viral infections (Occasional (29-5%)); Failure to thrive in infancy (Occasional (29-5%)); Partial IgA deficiency (Occasional (29-5%)); Abnormal facial shape (Very rare (<4-1%)); Hepatosplenomegaly (Very rare (<4-1%)); Hyperpigmentation of the skin (Very rare (<4-1%)); Rectovaginal fistula (Very rare (<4-1%)). 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-B+NK- severe combined immunodeficiency due to JAK3 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 JAK3 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.