X-Linked Agammaglobulinemia (2024)

Continuing Education Activity

X-linked agammaglobulinemia or XLA is a primary immunodeficiency disorder that prevents affected individuals from making antibodies and requires them to rely on lifelong immunoglobulin replacement therapy for survival. Without immunoglobulins (or antibodies), XLA patients are rendered vulnerable to invasive infections. Hospitalization for bacterial pneumonia, requiring intravenous antibiotics for resolution, is usually what prompts the diagnostic work-up for primary immunodeficiency. This activity reviews the pathophysiology of XLA and highlights the role of the interprofessional team in its management.

Objectives:

  • Identify the etiology of X-linked agammaglobulinemia.

  • Review the evaluation process for X-linked agammaglobulinemia.

  • Outline the treatment and management options available for X-linked agammaglobulinemia.

  • Summarize interprofessional team strategies for improving care coordination and communication to advance X-linked agammaglobulinemia and improve outcomes.

Access free multiple choice questions on this topic.

Introduction

X-linked agammaglobulinemia or XLA is one of the most common pediatric primary immunodeficiencies that prevent affected individuals from making antibodies and requires lifelong immunoglobulin replacement therapy for survival.[1]

The molecular basis for XLAis adisruption in B cell development due to mutation in Bruton's tyrosine kinase (Btk). Affected individualsinherita defect that preventsprecursor B cells in the bone marrow from forming mature, circulating B-lymphocytes that would otherwise be capable of proliferating and differentiating into antibody-producing plasma cells in secondary lymphoidorgans like thetonsils andlymph nodes. This dysfunction results indangerouslylow, clinically undetectablelevelsof all immunoglobulin isotypes in the serum.[2][3][4]

Without immunoglobulins (or antibodies),XLA patientsare rendered vulnerable to invasive infections from encapsulated bacteria (such as Streptococcus pneumoniae, Staphylococcus aureus,andHaemophilus influenzae), have an increased incidence of enterovirus infections(e.g., poliovirus, coxsackievirus, echovirus), and chronic diarrhea (fromGiardia lamblia).[5][6][7]

XLA patients commonly present with a history of recurrent upper respiratory tract infections, including sinusitis and otitis media, beginning after 6 to 9 months when most of the maternal antibodies have been exhausted. However, hospitalization for bacterial pneumonia, requiring intravenous antibiotics for resolution, is usually what prompts the diagnostic work-up for immune deficiency disease. The average age of diagnosis is 2.5 years, and almostall cases of XLA get diagnosed before5 years of age. Notably, late-onset forms of XLA also exist.[8]

There is currentlyno cure for XLA; however, early management with immunoglobulin replacement therapy andantibiotics to prevent and treat infections. Although this lifelong avenue is costly, it has been the mainstay of treatment for the past fifty years.Any significant delay in diagnosis posesthe danger of developing chronic, treatment-resistant infections, and end-organ damage that cannot be corrected.[9][3]

Etiology

XLA results from mutation of theBruton's tyrosine kinase gene (Btk)locatedon the long arm (q) of the X chromosome (Xq21.3-Xq22), affecting males almost exclusively. Hundreds ofdifferent mutationshave been reported to cause XLA,including missense, frameshift, deletion, insertion, premature stop codon, and pointmutations. The molecular location of these mutations encompassesbase pairs 101349447 to 101390796 on the X chromosome. However, no single mutation correlates with more than 3% of the known cases.[10][11]

The gene for Btk codes for a cytoplasmic tyrosine kinase protein, BTK,which acts as asignal transducer driving thefinal stages of B cell maturation. The inheritance of disease-causing mutation of the Btk gene interferes with BTK protein expression,resulting in the arrest of differentiation at thepre-B-cell stage in the bone marrow, causing a profound lack of mature B lymphocytes in the peripheral circulation anda corresponding absence or severe reductionin all immunoglobulin isotypesfromthe serum.[12]

Whilethe majority of agammaglobulinemia cases result from X-linked inheritance of Btk gene mutations, approximately 10% of the cases are the result of autosomal gene mutations. The resulting condition is known as autosomal recessive agammaglobulinemia(ARA) and describes the clinical phenotypeseen in femaleswith congenital agammaglobulinemia,which iscomparable to XLA in males. The molecular defects responsible forARA include mutations to the following genes:mu heavy chain (UGHN); gamma 5 (IGLL1); Igalpha (CD79A); Igbeta (CD79B); and BLNK. The wild-typeproteins encoded by these geneshave been shown tooperate in collaborationwith BTK,to promote the transition from pro-B-cells to pre-B-cells in the bone marrow, during B cell maturation.[13][14][10]

Epidemiology

XLA exclusively affects males. The reported incidence and prevalence of XLA vary considerably. Somesources reportthat XLAoccurs at a rate of 1 in 190000 live births with a frequency of 1 per 100000 newborn males, and an estimatedprevalenceof 1 to 9 per 1000000.[10] There isnoknown ethnic predisposition,but the reported incidence is highest in individuals of the White race.[15][16]

Common aliases for X-linked agammaglobulinemia include Bruton agammaglobulinemia, Btk agammaglobulinemia, Bruton tyrosine kinase agammaglobulinemia, agammaglobulinemia of Bruton, and congenital agammaglobulinemia.

Pathophysiology

When the disease-causing mutation affects a gene on the X chromosome, one copy of the mutant gene is sufficient to cause the condition. In theory, this means that XLA will affect50% of males born to mothers who are carriers. When the disease-causing mutations occur on geneswithin autosomes, either gender may be affected, e.g., females with autosomal recessive agammaglobulinemia.

Individuals with XLA haveone of severalinherited defectsin the Btk gene that interferes with the production of matureB-lymphocytesin circulation. T lymphocytesare unaffected.[3]

B cell development is a process that occurs in the bone marrow, where pro-B cells develop into pre-B cells before fully mature B cells enter the peripheral circulation. Normally, pre-B cells express the pre-BCR complex, which undergoes activation by BTK to initiate downstream signaling events involved in the maturation process. This process becomes blocked at the pre-B cell stage in individuals with inherited mutations that prevent BTK expression (figure 1). Western blotting or flow cytometry analysis of BTK protein expression in the monocytes or platelets of individuals with XLA demonstrates that it cannot be detected.[8][6]

Figure 1. Precursor B Cell-> Pro-B Cell-l X l- Pre-B Cell-> Immature B Cell

B cell differentiation becomes arrested at thePre-B cell stage with anassociated failure of immunoglobulin heavy chain rearrangement; this abrogates the production of immunoglobulins andprevents secondary lymphoid organs from developing fully.

Histopathology

Underdevelopment of lymphoid tissues, including the spleen, lymph nodes, tonsils, and Peyer's patches are visible on histology of tissue samples from patients with XLA. These findings, however, are not diagnostic of XLA.

History and Physical

A thoroughmedicalhistory and physical exam is a requirement for all individuals suspected of having XLA.

In the case of infants or very young children, history is elicited through a careful interview of the parents or caretakers. Obtaining information about the general health status, past infections, hospitalizations, surgeries, vaccinations, vaccination reactions, allergies, and current and past medications is crucial. Knowledge of the patient’s diet, home environment, social history, and travel activities may also be contributory.

A history of frequent, chronic, or recurrent infections, such as conjunctivitis, upper respiratory tract infections (e.g., pharyngitis; sinusitis; bronchitis; pneumonia), deep-seated skin infections (e.g., empyema), purulent otitis media, and diarrhea should raise suspicion. Patient records containing documented information of cultures found positive for encapsulated bacteria may help guide the diagnosis. Bacterial pneumonia, for example, is rare in infants and immunocompetent young children. Other important clues that can be used to direct the work-up include a historyindicating the need for IV antibioticsto resolve infections, multiple hospitalizations before the age of 3 years, ordevelopmentaldelay.[17][18]

A careful review of systems should be completed, withspecial attention paid to the upper and lower respiratory, lymphatic, gastrointestinal, and integumentary systems.

XLA infants are born healthy, with no outward signs of impending illness, and do not develop recurrent infections until 6-8 months of age when maternal antibodies are no longer active. Although a history of recurrent infections beginning after 6 months of age is very characteristic of this disease, a physical exam is also important. Lymphoid tissues aretypically hypoplastic in XLA patients.The tonsils may be difficult to visualize, and the cervical/inguinal lymph nodes may not be palpable. The otoscopic exam may be used to detect signs of chronic damage, i.e.,purulent otitis media, perforation of the tympanic membrane,or nasal discharge. Chest auscultation is performed to check for prolongation ofexpirationor inspiration, cough, any increase inrespiratory effort, or stridor. Audiblerhonchi, crackles, wheezing, and/or inspiratory squeaks suggestlungpathology and warrant further testing (e.g., lung function tests, CT scan, or biopsy) to rule outbronchiectasis. Similarly, the presence of abdominal distention justifies the need to perform an abdominal ultrasound to exclude hepatosplenomegaly.[1]

Finally, it is important not to overlook the family medical history, including information about past infections, hospitalizations, surgeries, previous diagnoses or symptoms of immunodeficiency, the ages and health status of living relatives, or causes of death.

Evaluation

The definitive laboratory evaluation of XLA involves quantitating serum immunoglobulin levels, enumerating lymphocyte subsets, performing provocative antibody response tests, and conducting molecular and genetic analyses.[19][20]

Atypicaldiagnostic test sequence would evaluate serum levels of IgG, IgM, and IgA, the number of CD19-positive or CD20-positive B cells in circulation, humoral vaccine responses, BTK protein expression in peripheral monocytes, and Btk gene sequencing.

Test results consistent with a diagnosis of XLA in a male patient with a history of recurrent bacterial infections would include finding:

  • Serum levels of IgG, IgM, and IgA that are more than two standard deviations below age-matched controls

  • Absence of mature B lymphocytes in the peripheral circulation (i.e., fewer than 1-2%)

  • Little or no increase in antibody titers 3-4 weeks afterprotein- or polysaccharide antigen vaccines(e.g.,immunizing against pneumococcal pneumonia or diphtheria-tetanus)

  • Low or absent BTK protein or mRNA expression levels

  • Detection of disease-causing mutations in the Btk gene

Researchers have isolated several different mutations in the Btk gene. The finding of Btk gene mutations alone does not constitute a diagnosis.[10][11]

Findings which suggest a diagnosis of XLA in males whose B cell levels are below the 1 to 2% thresholdinclude all or most of the following:

  • Ahistory of recurrent bacterial infections requiring one or more hospitalizations before the age of 5 years

  • Poor humoral responses to vaccines

  • No palpable tonsils or cervical lymph nodes

Tests with abnormal resultsshould berepeatedby independent testingfor confirmationbefore beginning treatment or seeking referrals.

Treatment / Management

There is no curative treatment for XLA. However, managementis by preventing, reducing,and treating infections.[3][1]

The optimalmanagement of patients with XLA includes[21][22][23][24][23][22]:

  • Regular immunoglobulin replacement therapy, using intravenous or subcutaneous infusions

  • Therapeutic and prophylactic use of antibioticsto treat and prevent bacterial infections

  • Careful monitoring tomanage reactions arising from immunoglobulin infusions, complications of infections, or the emergence of clinical disease (e.g., autoimmune, inflammatory, malignant)

  • Support (nutritional, social, psychological, and educational)

  • Counseling about the importance ofreceiving all available immunizations except for those containing live bacteria or viruses, e.g., polio (OPV, oral polio vaccine), measles/mumps/rubella (MMR), chickenpox (Varivax), BCG, yellow fever, androtavirus (Rota-Teq)

Intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) therapy requires several considerations:

  • A dose of 400 to 800 mg/kg every 3 to 4 weeks has been established to maintain an IgG trough greater than 5g/L.[25]Dose adjustments may be necessary for XLA patients with bronchiectasis and/or refractory infections such as meningoencephalitis.[17][26]

  • Both IVIG and SCIG are appropriate first-line therapies. IVIG may be preferred if a larger infusion volume due to a higher dose requirement is needed. SCIG has been reported to have a lower incidence of adverse reactions and allows for a more stable IgG trough following injection.[27]

  • Most adverse reactions are transient and pose no serious threat to the patient. These include immediate effects such as headache, fever, myalgia, hypo/hypertension, nausea, and chest pain. Reactions that resemble anaphylaxis are associated with higher transfusion ratesand occur during the infusion. Although IgA deficiency is associated with a risk of anaphylaxis during IVIG infusion, antibodies against IgA are unlikely in XLA patients due to agammaglobulinemia.Reactions may temporarily require cessation of the infusion untilsymptomatically managed withagents such as NSAIDs (for flushing, pain, and headache), diphenhydramine (for pruritus, rashes, and flushing),ondansetron (for nausea or vomiting) or muscle relaxants (for muscular spasm).

  • Delayed reactions are of greater concern, though less common, and include thromboembolism due to hyperviscosity, renal failure secondary to osmotic injury associated with sucrose-containing preparations, pseudohyponatremia, autoimmune hemolytic anemia, aseptic meningitis, and neutropenia.[28]

  • To avoid adverse reactions, it is appropriate to adhere to a regimen with appropriate premedications and rate of infusion that has been previously well-tolerated by the patient.

Differential Diagnosis

The differential diagnosis for XLA is:

  • Autosomal recessive agammaglobulinemia (ARA)

  • Common variable immunodeficiency disease (CVID)

  • Transient hypogammaglobulinemia of infancy (THI)

  • X-linked hyper IgM syndrome (Hyper-IgM)

  • X-linked lymphoproliferative disease (X-LPD)

  • Severe combined immunodeficiency disease (SCID)

Pertinent Studies and Ongoing Trials

Immunoglobulin replacement therapy has been used for decadesand continues to bethe core treatment modality for patients with XLA. Although there areisolated reports of successfulimmune reconstitution using stem cell transplants from HLA-identical donors as well as attempts at gene replacement therapy, these approaches are not currently standard of care due to risks outweighing benefits.[3][15][16][29]

Prognosis

Before regular immunoglobulin replacement therapy, most XLA died before the age of 10 from complications of lung disease, sepsis, or meningitis.Although chronic lung disease persists as an importantfactor in themortality in patients with XLA, life expectancyextends into adulthood.[23]Affected individuals who get diagnosed early (i.e., before five years of age) receive regular immunoglobulin replacement therapy and are prescribed antibiotics treat or prevent infections canbeexpected tohave anormal quality of life and live beyond the age of 40.[30]

Complications

XLA patients are at risk for complicationsof the diseaseitself as well as secondary to treatment.

Complications associated withXLAusually arise from infections, especiallythose that have become recurrent.Susceptible individuals can becomechronically illand sufferorgan damage. For example, repeated episodes of acute pneumoniamay culminate inchronic lung diseaseand lead to bronchiectasis,which hasthe potentialto reducelife expectancy. The likelihoodthat chronic infectionswill evolve into serious, life-threatening conditions increases with the length of delay in diagnosis. The later treatment begins, the more difficult itis to eradicate the causative organismsand prevent the systemic spread of infection to joints and vital organs.[7]

Complications associated withchronic infections are, by far, the most common problemconfronted by patients withXLA. Other, less commoncomplications include the increasedrisk of developingmalignancy,inflammatory conditions,orautoimmune disease.

Complications associated withtreatment are mainly those which arise from immunoglobulin replacement therapy. The replacement of immunoglobulin is a lifelong requirement for individuals with XLA.Indeed, regular immunoglobulin replacement therapy is known to increase life expectancy,lower therate and severity of infections, decrease the number of hospitalizations,andreduce the need for antibiotics. Unfortunately, it also correlates with side effectsand must, therefore, have careful monitoring. Clinicians can overcome complications associated with immunoglobulin replacement therapy by changing (1) the time interval between immunoglobulin infusions,(2) the route of administration, (3) the rate of administration, or (4) the product used for replacement.[31]

Immunoglobulins usedin therapy derive from the pooled serum of thousands of healthy donors who have had screening for transmissible diseases. The donor serum is processedto retain maximal amounts ofIgGand only trace amounts of IgA and IgM, thus reducingthe likelihood of triggering anaphylactic reactions to IgA ordevelopingkidney damage from complex formation induced by IgM.

The length oftime between infusionsvaries according tothe route of administration. The two most common routes of administering immunoglobulins are intravenous (IVIG)and subcutaneous (SCIG). The interval between IVIG infusions can be as long asa month, while the maximum interval between SCIG infusionsis usually no more thana week.[32][33]

The rate of delivery and hence, the final immunoglobulin concentration obtained is another important factor. Thehigher the rate of delivery, the greater the likelihood of complications. In situations wherehigher immunoglobulin levelsare needed to combat a recalcitrantinfection, the clinician must balance the decision to increase the infusion rate against the side effect profile.

Differences in theexact composition of the product used for immunoglobulinreplacement also contributes to tolerability. Thepurity and constituents (i.e., additives used to reduce the aggregate formation and enhance delivery) vary according to the manufacturer, and the reactions elicited vary in different individuals.

Reactions to immunoglobulin infusion therapycanbe immediate or latent.The most common immediate side effect is a headache. Headache occurs within minutes and is managedusing over-the-counter medications, althoughit can often be avoidedaltogether by simplyslowing the rate of infusion.

Other commoninfusion reactions includenausea, malaise, fever/chills, chest tightness, and migraines. Infusion reactions can also categorize according to the system affected. Cardiovascular reactions includetachycardia, palpitations, flushing, andhypotension; neurologic reactionsinclude anxiety, nervousness, irritability, tremor, fainting andseizures; respiratory system reactions includecough, chest tightness, dyspnea, wheezing, and bronchospasm; dermatologic reactions include erythema, urticaria, and eczema; musculoskeletal reactions include low backache, arthralgia, and myalgia; and gastrointestinal reactions includeabdominal pain, distention, and liver dysfunction.

Moreserious complications can alsoarise. These are much less common and occurafter a period of latency.Examples include aseptic meningitis, anaphylactic reactions, Stevens-Johnson syndrome, erythema multiforme, acute renal failure, acute respiratory distress syndrome, transfusion-associated lung injury,deep vein thrombosis, pulmonary edema, pulmonary embolism, cardiac arrest, shock, coma.[34]

Deterrence and Patient Education

Patients and their families shouldbe providedresources and educational materials informing them about vaccines, immunoglobulin replacement therapy, prophylactic and therapeutic use of antibiotics, routine and emergency medical care, the importance of keeping follow-up appointments,healthcare team specialists,preparation fortraveling, the importance of record-keeping, support, andhow to become a goodpatient advocate.

Reasons for avoidinglive virus vaccines,such as oral polio, mumps, measles, rubella, rotavirus, yellow fever, chickenpox, should be explainedthoroughly.

Patients and families shouldbe given the following advice when planninga trip:

Carry a portable water filtration system, prophylactic antibiotics, and other medications;

Know thevaccination requirementsfor traveling to foreign countries; be prepared to comply or obtain formal exemptions;

Carry an approved list of resources, includingthe locations, contact information, hours of operation, for:

  • infusion centers (to avoid interruption in the regular immunoglobulin replacement regimen)

  • physicians and pharmacists (to obtain antibiotics needed to combat new infections)

  • hospitals, medical specialists, emergency centers, therapists, and other support personnel

Record keeping should be encouraged.All aspects of patient care, management,and follow-up should be included, as well as a list of contacts and resources that arehelpful to the patient.

Information regardingthe patient'svaccination record, infection history, doctor/emergency department visits, hospitalizations, illnesses, days missed from school, therapist- and in-home care provider visits, lab test results, growth record, allergies, sensitivities, dietary preferences, medications, supplements; travel record, and social contacts and activities should be recorded.

Pearls and Other Issues

  • Early diagnosis is key in decreasing morbidity and mortality of patients with XLA

  • Characterized by mutation of Btk, which prevents maturation of B-lymphocytes and subsequently the production of circulating immunoglobulin, resulting in severely impaired humoral immunity

  • Look for a male infant or toddler (who no longer has protection from maternal IgG) with recurrent encapsulated organism infections requiring frequent hospitalizations and intravenous antibiotics

  • Recurrent sinusitis, otitis, pneumonia, gastroenteritis

  • Laboratory investigation reveals absent or very low levels of mature B-lymphocytes and circulating immunoglobulin

  • The current mainstay of treatment is withintravenous immunoglobulin

  • Avoid live vaccines

Enhancing Healthcare Team Outcomes

XLA is one of the most common primary immunodeficiencies occurring in the pediatric population. Males over the age of 6 months present with recurrent infections due to encapsulated organisms because they lack the ability to produce mature B-lymphocytes and subsequently circulating immunoglobulin. This disease does not present at birth because maternal IgG provides immune defense during the earliest months of life. The initial presentations of XLA occur most commonly in the pediatric primary care and inpatient hospitalist settings. The involvement of multiple disciplines is vital to improving the outcomes of patients with XLA so that diagnosis can take place as early as possible, with streamlined treatment.

Appropriate care team members for a patient with XLA would most likely include a pediatrician,immunologist, and pulmonologist, as well as other specialists who can contribute to the care of complications and comorbidities associated with XLA. Pathologists and radiologists can aid in the early diagnosis of XLA, while pharmacists can help clinicians select appropriate treatment regimens and perform medication reconciliation. Nursing should be able to counsel the family, answer questions, and assess the progress of treatment. This interprofessional team approach will lead to better outcomes, and give the family/patient more resources form which to access care and information about XLA. [Level V]

Family members or caretakers should be encouraged to take part in the patient’s care and learn how to become effective patient advocates, with the goal of transferring advocacy skills to the patient.

Records should also include a useful contactlist regardinghealthcare team members, for physicians, staff, physician assistants,therapists, nurses, specialists, specialty centers (e.g., for immunoglobulin replacement therapy), hospitals, pharmacies, support groups, and insurance providers.

The patient needs to understand the necessity for regular follow-up visits. Patients should receive advance information regarding the specialists that they need to see, the tests that are necessary (e.g. routine blood tests, determination of lymphocyte subsets and immunoglobulin levels; liver function tests; hepatitis screening; pulmonary function tests; CT scans) and therole that the resulting information willplay in monitoring treatment responses and stemming disease progression.

Randomized-controlled trials (RCTs) supporting the best treatment methods are very limited due to the rare nature of XLA. Additionally,the poor prognosis associated with a lack of treatmentethically preventssuch studies. Current recommendations are made based on an exhaustive review of currentcase reports and case series of XLA cases from peer-reviewed journals, as well as small RCTs regarding the treatment of primary immunodeficiencies in general. Expert opinion from an interprofessional team may be necessary when current evidence fails to provide a definitive recommendation for treatment modalities.

Overall, an interprofessional team approach to the treatment of patients with XLA is the proper management methodology.

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Disclosure: Alexandra Lackey declares no relevant financial relationships with ineligible companies.

Disclosure: Faran Ahmad declares no relevant financial relationships with ineligible companies.

X-Linked Agammaglobulinemia (2024)

FAQs

X-Linked Agammaglobulinemia? ›

X-linked agammaglobulinemia or XLA is a primary immunodeficiency

primary immunodeficiency
Syndromic primary immunodeficiencies (sPIDs) are conditions with features of inborn errors of immunity (IEI) overlapping with other multisystem clinical manifestations, which are not directly associated with the immunologic deficit [1].
https://www.ncbi.nlm.nih.gov › pmc › articles › PMC10419544
disorder that prevents affected individuals from making antibodies and requires them to rely on lifelong immunoglobulin replacement therapy for survival. Without immunoglobulins (or antibodies), XLA patients are rendered vulnerable to invasive infections.

What is the main concern for patients with X-linked agammaglobulinemia? ›

X-linked agammaglobulinemia (a-gam-uh-glob-u-lih-NEE-me-uh), also called XLA, is an immune system disorder that's passed through families, called inherited. XLA makes it hard to fight infections. People with XLA might get infections of the inner ear, sinuses, respiratory tract, bloodstream and internal organs.

What is X-linked agammaglobulinemia characterized by? ›

X-linked agammaglobulinemia (XLA) is characterized by recurrent bacterial infections in affected males in the first two years of life. Recurrent otitis is the most common infection prior to diagnosis.

What is the life expectancy of someone with XLA? ›

Most men with X-linked agammaglobulinemia (XLA) live into their 40s. The prognosis is better if treatment is started early, ideally if intravenous immunoglobulin G (IVIG) is started before the individual is aged 5 years.

What is XLA caused by? ›

XLA is an inherited immune disorder caused by an inability to produce B cells or the immunoglobulins (antibodies) that the B cells make. XLA is also called Bruton type agammaglobulinemia, X-linked infantile agammaglobulinemia, and congenital agammaglobulinemia.

What are X-linked agammaglobulinemia symptoms? ›

What are the symptoms of X-linked agammaglobulinemia?
  • Sinusitis, rhinitis (nasal infection)
  • Pyoderma (skin infection)
  • Conjunctivitis (eye infection)
  • Osteomyelitis (bone infection)
  • Meningitis (spinal cord infection)
  • Sepsis (bloodstream infection)
  • Bronchitis (bronchial infection)
  • Pneumonia (lung infection)

What are the symptoms of X-linked? ›

What are the symptoms of X-linked agammaglobulinemia?
  • nasal infections.
  • skin infections.
  • bone infections.
  • eye infections (including pink eye)
  • meningitis.
  • bronchitis.
  • sepsis, or infection of the blood stream.
  • pneumonia.

How do you treat X-linked agammaglobulinemia? ›

Medicines to treat XLA include:
  1. Gammaglobulin. This is a type of protein found in blood that contains antibodies against infections. It's put into a vein, called infusion, every 2 to 4 weeks or given with weekly shots. ...
  2. Antibiotics. Some people with XLA take antibiotics all the time to prevent infections.
Jan 10, 2024

How rare is X-linked agammaglobulinemia? ›

X-linked agammaglobulinemia is rare. It's more common in babies and kids AMAB. Approximately 1 in 200,000 male babies are born with XLA.

What is the most common organism in X-linked agammaglobulinemia? ›

More than 50% of children with X-linked agammaglobulinemia have had serious infections within their first two years of life. Pyogenic encapsulated bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, are the most commonly isolated pathogens in patients with XLA.

Is XLA a rare disease? ›

About X-linked agammaglobulinemia

Population Estimate:Fewer than 5,000 people in the U.S. have thisdisease. Symptoms:May start to appear as a Child. Cause:This disease is caused by a change in the genetic material (DNA).

What infections do patients with agammaglobulinemia get recurrent? ›

Hemophilus influenzae is the most common mucous- producing infection (pyogenic) that occurs in people with X-linked agammaglobulinemia. Children may also have repeated infections with pneumococci, streptococci, and staphylococci bacteria, and infrequently pseudomonas infections.

Why does XLA only affect males? ›

This condition is inherited in an X-linked recessive pattern . The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition.

How to test for XLA? ›

Laboratory Studies. Perform initial studies measuring quantitative IgG, IgM, immunoglobulin E (IgE), and immunoglobulin A (IgA) levels. IgG levels should be measured first, preferably after age 6 months, when maternal levels decline. IgG levels below 100 mg/dL are usually indicative of X-linked agammaglobulinemia (XLA) ...

What are the complications of XLA? ›

Complications of HLH disease
  • Nervous system problems.
  • An enlarged spleen.
  • Liver and lung damage.

Is agammaglobulinemia autoimmune? ›

In addition to lacking B cells, some people with XLA may also have low neutrophil counts and may develop a rare form of arthritis. Although infrequent, some with antibody deficiency with absent B cells may develop autoimmune or central nervous system disease.

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