XLA diagnosis usually begins due to a history of recurrent infections, mostly in the respiratory tract, through childhood. This is due to humoral immunodeficiency. The diagnosis is probable when blood tests show the complete lack of circulating B cells (determined by the B cell marker CD19 and/or CD20), as well as low levels of all antibody classes, including IgG, IgA, IgM, IgE and IgD.

When XLA is suspected, it is possible to do a Western Blot test to determine whether the Btk protein is being expressed. Results of a genetic blood test confirm the diagnosis and will identify the specific Btk mutation, however its cost prohibits its use in routine screening for all pregnancies. Women with an XLA patient in their family should seek genetic counseling before pregnancy.Although the symptoms of a XLA and other primary immune diseases (PID) include repeated and often severe infections, the average time for a diagnosis of a PID can be up to 10 years.

The basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte and granulocyte counts) and immunoglobulin levels (the three most important types of antibodies: IgG, IgA and IgM).

Other tests are performed depending on the suspected disorder:

- Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocytes): different groups of T lymphocytes (dependent on their cell surface markers, e.g. CD4+, CD8+, CD3+, TCRαβ and TCRγδ), groups of B lymphocytes (CD19, CD20, CD21 and Immunoglobulin), natural killer cells and monocytes (CD15+), as well as activation markers (HLA-DR, CD25, CD80 (B cells).

- Tests for T cell function: skin tests for delayed-type hypersensitivity, cell responses to mitogens and allogeneic cells, cytokine production by cells

- Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses

- Tests for phagocyte function: reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity.

Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.

Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease are present, but not all.

The mainstay of treatment consists of thymectomy and immunoglobulin replacement with IVIG (Kelesidis, 2010). Immunodeficiency does not resolve after thymectomy (Arnold, 2015). To treat the autoimmune component of the disease, immune-suppression is sometimes used and it is often challenging to determine if a patient’s symptoms are infectious or autoimmune (Arnold, 2015).

Patients should have serological testing for antibodies to toxoplasma and cytomegalovirus. If receiving a transfusion, CMV negative blood should be used in those with negative serological testing. Live vaccines should also be avoided (Kelesidis, 2010). The CDC recommends pneumococcal, meningococcal, and Hib vaccination in those with diminished humoral and cell-mediated immunity (Hamborsky, 2015).

Some have advocated treating prophylactically with TMP-SMX if CD4 counts are lower than 200 cells/mm^3, similar to AIDS patients (Kelesidis, 2010).

There are no formal diagnostic criteria (Kelleher, 2003) and many informal definitions exist. Most commonly thymoma is present with mixed humoral and cellular immune deficiency. T and B cells are both depleted so patients suffer from both encapsulated organisms as well as opportunistic infections (Miyakis, 2005). Some have defined GS as a subset of common variable immunodeficiency (CVID). Unlike CVID, there are reduced B cells in the periphery in GS (Kelesidis, 2010).

More generally it can be defined as an adult-onset primary immunodeficiency associated with thymoma, hypogammaglobulinemia, diminished B and T cells, and inverted CD4/CD8+ ratio(Kelesidis, 2010).

Typically, diagnosis involves several preliminary tests of immune function, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels.

In the case of LAD-I, specific diagnosis is done by flow cytometry. This technique will reveal absent or reduced CD18 expression in the leukocyte membrane. Recently, prenatal diagnosis systems has been established, allowing an early detection of the disease.

LAD-II diagnosis includes the study of different glycosilated forms of the transferrin protein. In LAD-III, as platelet function is also affected, this could be used to differentiate it from the other types.

Available treatment falls into two modalities: treating infections and boosting the immune system.

Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised. In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administrated, resulting in higher Ig levels for about three to four weeks, although this varies with each patient.

Serology (detection on antibodies to a specific pathogen or antigen) is often used to diagnose viral diseases. Because XLA patients lack antibodies, these tests always give a negative result regardless of their real condition. This applies to standard HIV tests. Special blood tests (such as the western blot based test) are required for proper viral diagnosis in XLA patients.

It is not recommended and dangerous for XLA patients to receive live attenuated vaccines such as live polio, or the measles, mumps, rubella (MMR vaccine). Special emphasis is given to avoiding the oral live attenuated SABIN-type polio vaccine that has been reported to cause polio to XLA patients. Furthermore, it is not known if active vaccines in general have any beneficial effect on XLA patients as they lack normal ability to maintain immune memory.

XLA patients are specifically susceptible to viruses of the Enterovirus family, and mostly to: polio virus, coxsackie virus (hand, foot, and mouth disease) and Echoviruses. These may cause severe central nervous system conditions as chronic encephalitis, meningitis and death. An experimental anti-viral agent, pleconaril, is active against picornaviruses. XLA patients, however, are apparently immune to the Epstein-Barr virus (EBV), as they lack mature B cells (and so HLA co-receptors) needed for the viral infection. Patients with XLA are also more likely to have a history of septic arthritis.

It is not known if XLA patients are able to generate an allergic reaction, as they lack functional IgE antibodies.There is no special hazard for XLA patients in dealing with pets or outdoor activities. Unlike in other primary immunodeficiencies XLA patients are at no greater risk for developing autoimmune illnesses.

Agammaglobulinemia (XLA) is similar to the primary immunodeficiency disorder Hypogammaglobulinemia (CVID), and their clinical conditions and treatment are almost identical. However, while XLA is a congenital disorder, with known genetic causes, CVID may occur in adulthood and its causes are not yet understood.

XLA was also historically mistaken as Severe Combined Immunodeficiency (SCID), a much more severe immune deficiency ("Bubble boys").A strain of laboratory mouse, XID, is used to study XLA. These mice have a mutated version of the mouse Btk gene, and exhibit a similar, yet milder, immune deficiency as in XLA.

In terms of diagnosis of "humoral immune deficiency" depends upon the following:

- Measure "serum immunoglobulin levels"

- B cell count

- Family medical history

Treatment for "B cell deficiency"(humoral immune deficiency) depends on the cause, however generally the following applies:

- Treatment of infection(antibiotics)

- Surveillance for malignancies

- Immunoglobulin replacement therapy

The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be either genetic or acquired by malnutrition and poor sanitary conditions. Only for some genetic causes, the exact genes are known. Although there is no true discrimination to who this disease affects, the genes are passed from mother to child, and on occasion from father to child. Women tend not to show symptoms due to their second X chromosome not having the mutation while man are symptomatic, due to having one X chromosome.

The diagnosis of T cell deficiency can be ascertained in those individuals with this condition via the following:

- Delayed hypersensitivity skin test

- T cell count

- Detection via culture(infection)

The International Union of Immunological Societies recognizes nine classes of primary immunodeficiencies, totaling over 120 conditions. A 2014 update of the classification guide added a 9th category and added 30 new gene defects from the prior 2009 version.

Complete or partial deficiency

- "Complete insufficiency" of T cell function can result from hereditary conditions (also called primary conditions) such as severe combined immunodeficiency (SCID), Omenn syndrome, and cartilage–hair hypoplasia.

- "Partial insufficiencies" of T cell function include acquired immune deficiency syndrome (AIDS), and hereditary conditions such as DiGeorge syndrome (DGS), chromosomal breakage syndromes (CBSs), and B-cell and T-cell combined disorders such as ataxia-telangiectasia (AT) and Wiskott–Aldrich syndrome (WAS).

- "Primary (or hereditary) immunodeficiencies" of T cells include some that cause complete insufficiency of T cells, such as severe combined immunodeficiency (SCID), Omenn syndrome, and Cartilage–hair hypoplasia.

- "Secondary causes" are more common than primary ones. Secondary (or acquired) causes are mainly:

A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), 75% of the children were still alive.

Combined immunodeficiencies (or combined immunity deficiency) are immunodeficiency disorders that involve multiple components of the immune system, including both humoral immunity and cell-mediated immunity.

This category includes conditions such as bare lymphocyte syndrome, as well as severe combined immunodeficiency.

ICD-9 divides immune deficiencies into three categories: humoral (279.0), cell-mediated (279.1), and combined (279.2). However, ICD-10 does not include a category for cell-mediated immune dysfunction (antibody is D80, and combined is D81), thus grouping T-cell mediated conditions with combined conditions.

Once a diagnosis is made, each individual's treatment is based on an individual’s clinical condition. Hematopoietic stem cell transplant is a possible treatment of this condition but its effectiveness is unproven.

Additionally, magnesium supplementation is a promising potential treatment for XMEN. One of the consequences of loss of "MAGT1" function is a decreased level of unbound intracellular Mg2+. This decrease leads to loss of expression of an immune cell receptor called "NKG2D", which is involved in EBV-immunity. Remarkably, Mg2+ supplementation can restore "NKG2D" expression and other functions that are abnormal in patients with XMEN. Early evidence suggests continuous oral magnesium threonate supplementation is safe and well tolerated. Nonetheless, further research is needed to evaluate the use of Mg2+ as a treatment for XMEN. It remains unclear if such supplementation will protect against the development of lymphoma in patients with XMEN. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

For this condition, differential diagnosis sees that the following should be considered:

- CD25 deficiency

- STAT5b deficiency

- Severe immunodeficiency(combined)

- X-linked thrombocytopenia

Though BLSII is an attractive candidate for gene therapy, bone marrow transplant is currently the only treatment.

Diagnosis for "type 1" of this condition for example, sees that the following methods/tests are available:

- Endoscopic

- CT scan

- Histologic test

Once a diagnosis is made, the treatment is based on an individual’s clinical condition. Based on the apparent activation of the mTOR pathway, Lucas and colleagues treated patients with rapamycin, an mTOR inhibitor. This effectively reduced hepatosplenomegaly and lymphadenopathy, most likely by restoring the normal balance of naïve, effector, and memory cells in the patients’ immune system. More research is needed to determine the most effective timing and dosage of this medication and to investigate other treatment options. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.

XMEN patients generally have chronically high levels of EBV with increased EBV-infected cells, diminished thymic output of CD4+ cells, reduced CD4:CD8 ratio, moderately high B cell counts, and mild neutropenia. Their neutropenia may be related to their chronic EBV. Some patients also showed defective T cell proliferation in response to mitogen stimulation, variable immunoglobulin deficiencies, or deficient vaccination response.

An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:

- By the component(s) of the immune system affected

- By whether the immune system is overactive or underactive

- By whether the condition is congenital or acquired

According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immunodeficiencies exceeds the number of PIDs.

It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.

Generally accepted reference range for absolute neutrophil count (ANC) in adults is 1500 to 8000 cells per microliter (µl) of blood. Three general guidelines are used to classify the severity of neutropenia based on the ANC (expressed below in cells/µl):

- Mild neutropenia (1000 <= ANC < 1500): minimal risk of infection

- Moderate neutropenia (500 <= ANC < 1000): moderate risk of infection

- Severe neutropenia (ANC < 500): severe risk of infection.

Each of these are either derived from laboratory tests or via the formula below:

ANC = formula_1