Materiały źródłowe

• #1 X-linked Agammaglobulinemia | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/x-linked-agammaglobulinemia

  The symptoms of X-linked agammaglobulinemia usually become apparent in the first 6 to 9 months of age, but can present as late as 3 to 5 years of age. The following are the most common symptoms of X-linked agammaglobulinemia. However, each child may experience symptoms differently. Symptoms may include: […] Numerous, serious, and/or life-threatening illnesses, including, but not limited to, the following: […] Cancers, including leukemia, lymphoma, and colon cancer, have been reported in a small percentage of older patients with X-linked agammaglobulinemia. […] Without antibody replacement, these children could die at an early age from severe infections. Children who develop chronic lung disease with bronchiectasis (widening and scarring of the airways) may have a shortened lifespan, in some cases. However, those children with X-linked agammaglobulinemia who are diagnosed and treated early should be able to lead normal, active lives.

• #1 X-linked agammaglobulinemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/x-linked-agammaglobulinemia/symptoms-causes/syc-20361635

  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. […] Most babies with XLA appear healthy for the first few months. They’re protected by the proteins called antibodies they got from their mothers before birth. […] When these antibodies leave their systems, the babies begin to get repeat bacterial infections. The infections can be life-threatening. Infections might involve the ears, lungs, sinuses and skin. […] Male infants born with XLA have very small tonsils and small or no lymph nodes. […] People with XLA can live mostly typical lives. They should try to take part in regular activities for their ages. But repeat infections linked to XLA will likely need careful watching and treatment. They can damage organs and be life-threatening.

• #1 X-Linked Agammaglobulinemia (XLA) | NIAID: National Institute of Allergy and Infectious Diseases

  https://www.niaid.nih.gov/diseases-conditions/x-linked-agammaglobulinemia

  Infants with XLA develop frequent infections of the ears, throat, lungs, and sinuses. Serious infections also can develop in the bloodstream, central nervous system, skin, and internal organs. […] These children tend to cope well with most short-term viral infections but are very susceptible to chronic viral infections such as hepatitis. They usually lack or have very small tonsils. […] People with XLA have extremely low numbers of B cells, and blood tests will show extremely low levels of all types of immunoglobulins (antibodies). People with XLA fail to develop antibodies to specific germs and will not produce protective antibodies after immunizations.

• #1 X-Linked Agammaglobulinemia: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/24955-x-linked-agammaglobulinemia

  People with X-linked agammaglobulinemia usually have small or missing lymph nodes, tonsils and adenoids due to their underdeveloped immune systems. They experience frequent bacterial infections in childhood, including: […] Changes in your BTK gene mean you cant fight off illness the same way someone without the mutation can. This means you get sick frequently, sometimes with life-threatening illnesses. […] People with XLA need treatment for the rest of their lives so theyre less vulnerable to illness. Theyll need to work closely with their healthcare provider to treat any illnesses as soon as possible. You or your child can expect to miss more days of school and work due to illness than others. […] Thanks to advances in treatment, people with XLA live into adulthood in developed countries like the U.S. In still-developing countries, getting a diagnosis and treatment is much harder. This usually means children with XLA dont live as long.

• #1 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  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. […] 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 almost all cases of XLA get diagnosed before 5 years of age. Notably, late-onset forms of XLA also exist.

• #1 X-Linked (Bruton) Agammaglobulinemia Clinical Presentation: History, Physical Examination, Complications

  https://emedicine.medscape.com/article/1050956-clinical

  Recurrent infections begin in infancy and persist throughout adulthood. […] The most common presentation of X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is increased susceptibility to encapsulated pyogenic bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas species. […] Skin infections in patients with XLA are mostly caused by group A streptococci and Staphylococcus aureus, and they can present as impetigo, cellulitis, abscesses, or furuncles. […] A form of eczema that resembles atopic dermatitis may be evident, along with an increased incidence of pyoderma gangrenosum, vitiligo, alopecia totalis, and Stevens-Johnson syndrome (from increased use of medications). […] Other infections that commonly present with XLA include enteroviral infections, sepsis, meningitis, and bacterial diarrhea (often caused by common organisms, such as Campylobacter jejuni and Giardia species).

• #1 What is X-Linked Agammaglobulinemia (XLA)?

  https://www.myigsource.com/x-linked-agammaglobulinemia

  People with XLA develop frequent infections involving the: sinuses, ears, lungs. […] They may also develop infections of the bloodstream and internal organs. Gastrointestinal and skin infections can also be a problem. […] Doctors may find that people with XLA have very small tonsils and lymph nodes (glands of the neck). This is because tonsils and lymph nodes are made up of B lymphocytes. In people with XLA, the size of these tissues are reduced because of the absence of B lymphocytes.

• #1

  https://link.springer.com/article/10.1007/s10875-023-01502-x

  To understand the natural history and clinical outcomes for patients with X-linked agammaglobulinemia (XLA) in the United States utilizing the United States Immunodeficiency Network (USIDNET) patient registry. […] The respiratory tract was the most affected organ system (51.2% of patients) followed by gastrointestinal (40%), neurological (35.4%), and musculoskeletal (28.3%). Infections were common both before and after diagnosis, despite IgGR therapy. […] Current therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function. […] Neurologic condition was the most common underlying co-morbidity for those XLA patients who died. […] Symptoms of allergic disease such as chronic rhinitis, eczema/atopic dermatitis, and urticaria were reported in 28% of patients.

• #1 Orphanet: X-linked agammaglobulinemia

  https://www.orpha.net/en/disease/detail/47

  A clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, characterized in affected males by recurrent bacterial infections during infancy. […] Affected individuals are usually healthy in the first few months of life due to residual maternal immunoglobulins. The majority of patients develop recurrent or persistent bacterial infections, most commonly caused by S. pneumoniae and H. influenzae, within the first two years of life: otitis media, conjunctivitis, sinusitis, respiratory infections, diarrhea and skin infections (impetigo, cellulitis, abscesses, and furuncles). Other severe infections may include empyema, meningitis, sepsis, or septic arthritis. Pyoderma or cellulitis (associated with neutropenia) and pseudomonas or staphylococcal sepsis are frequent presenting findings, particularly in patients less than 12 months of age.

• #1 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics 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 poses the danger of developing chronic, treatment-resistant infections, and end-organ damage that cannot be corrected. […] Complications associated with XLA usually arise from infections, especially those that have become recurrent. Susceptible individuals can become chronically ill and suffer organ damage. For example, repeated episodes of acute pneumonia may culminate in chronic lung disease and lead to bronchiectasis, which has the potential to reduce life expectancy. The likelihood that chronic infections will evolve into serious, life-threatening conditions increases with the length of delay in diagnosis. The later treatment begins, the more difficult it is to eradicate the causative organisms and prevent the systemic spread of infection to joints and vital organs.

• #1 Mortality and morbidity in patients with X-linked agammaglobulinaemia | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-mortality-morbidity-in-patients-with-S0301054613002863

  X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. […] Among 41 patients, 26.8% died during the follow up period. […] The most common first presentation was pneumonia in 10 patients, chronic otitis media in seven (17.0%), and diarrhoea in five (12.1%). […] The main cause of mortality in our patients was respiratory failure due to the chronic respiratory infections which suggests that, despite appropriate serum IgG level of patients during follow-up period, chronic lung disease (CLD) remains the most dangerous complication in XLA patients.

• #1 X-Linked Agammaglobulinemia in Children – Stanford Medicine Children’s Health

  https://www.stanfordchildrens.org/en/topic/default?id=x-linked-agammaglobulinemia-in-children-90-P01666

  Breakdown of red blood cells (autoimmune hemolytic anemia) […] Kidney inflammation (glomerulonephritis) […] Fewer white blood cells called neutrophils (neutropenia) […] Skin and muscle inflammation (dermatomyositis). A few older children with this disease may have cancers such as leukemia, lymphoma, or colon cancer. Without antibody replacement, a child with this disease could die at an early age from severe infections. Some children who get chronic lung disease with widening and scarring of the airways (bronchiectasis) may have a shortened lifespan. But most children with X-linked agammaglobulinemia who are treated early can lead normal, active lives.

• #1 X-Linked (Bruton) Agammaglobulinemia Clinical Presentation: History, Physical Examination, Complications

  https://emedicine.medscape.com/article/1050956-clinical

  Individuals who are affected may have an increased incidence of autoimmune diseases leading to thrombocytopenia, neutropenia, hemolytic anemia, and rheumatoid arthritis. […] Persistent enteroviral infections may rarely lead to fatal encephalitis or a dermatomyositis-meningoencephalitis syndrome. […] Males affected with XLA usually present when they are younger than 1 year with unusually severe and/or recurrent otitis media, sinopulmonary infections, and pneumonia. […] For children younger than 12 years, typical infections are caused by encapsulated bacteria. […] In adulthood, skin manifestations become more common, usually due to Staphylococcus and group A Streptococcus organisms. […] Both infants and adults can have autoimmune diseases associated with XLA. […] Diarrhea is common and is caused by Giardia or Campylobacter species. […] Patients with XLA are prone to enteroviral infections, including poliovirus. […] Complications for patients with XLA include chronic sinopulmonary infections, enteroviral infections of the central nervous system, increased occurrence of autoimmune diseases, and skin infections.

• #1

  https://link.springer.com/article/10.1007/s10875-023-01502-x

  In this cohort, 222 patients (92.5%) reported infections, with 1054 total infections reported in the Registry. […] After diagnosis, 178 patients reported any medical condition: 89 patients (50%) reported four or more conditions, 40 (22%) reported 1 condition, 28 (15.7%) reported two conditions, and 21 (11.8%) reported 3 conditions. […] The most common underlying co-morbid conditions in these deceased patients were neurologic (75%), followed by respiratory (70%). […] Mortality in the past 20 years appears improved among this US cohort, with only one death since 2000.

• #1 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  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 important factor in the mortality in patients with XLA, life expectancy extends into adulthood. Affected individuals who get diagnosed early (i.e., before five years of age) receive regular immunoglobulin replacement therapy and are prescribed antibiotics to treat or prevent infections can be expected to have a normal quality of life and live beyond the age of 40.

• #1 Orphanet: X-linked agammaglobulinemia

  https://www.orpha.net/en/disease/detail/47

  Infections tend to persist throughout adulthood. Affected patients are reported to have a higher susceptibility to severe and chronic enteroviral infections. […] Some patients have a less severe clinical presentation and are not recognized as immunodeficient until 10 years of age or later. Complications of X-linked agammaglobulinemia (XLA) include progressive lung disease, chronic sinusitis, inflammatory bowel disease, arthritis, as well as neurological changes. […] Most patients with XLA lead a normal life. Life expectancy may be reduced in some patients as a result of complications such as severe infections and chronic pulmonary damage. Early therapeutic measures and treatment compliance are major prognostic factors.

• #1 X-Linked Agammaglobulinemia | Loma Linda University Children’s Health

  https://lluch.org/conditions/x-linked-agammaglobulinemia

  A few older children with this disease may have cancers such as leukemia, lymphoma, or colon cancer. […] Without antibody replacement, a child with this disease could die at an early age from severe infections. Some children who get chronic lung disease with widening and scarring of the airways (bronchiectasis) may have a shortened lifespan. But most children with X-linked agammaglobulinemia who are treated early can lead normal, active lives. […] Most children with X-linked agammaglobulinemia who are treated early can lead normal, active lives.

• #1 X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-6-5

  2 patients previously diagnosed with CVID associated with virtual absence of CD19+ B cells were reclassified as having a delayed diagnosis and adult-presentation of XLA. Patient 1, a 64 yr old male with recurrent sinobronchial infections had a low level of serum IgG of 360 mg/dl (normal 7361900), IgA 27 mg/dl (normal 90474), and IgM 25 mg/dl (normal 50415). Patient 2, a 46 yr old male with recurrent sinopulmonary infections had low IgG of 260 mg/dl, low IgA 16 mg/dl, and normal IgM. […] These two cases represent an unusual adult-presentation of XLA, a humoral immunodeficiency usually diagnosed in childhood and the need to further investigate a suspicion of XLA in adult males with CVID particularly those associated with low to absent CD19+ B cells. […] In patients with XLA, typically immunological evaluation shows marked deficiency or absence of CD19+ B lymphocytes and severely decreased levels of all isotypes of immunoglobulins, however wide variability in clinical presentation among families with XLA have been observed.

• #1 Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

  https://www.mdpi.com/2227-9059/11/3/959

  We present a unique and unusual case of a male patient diagnosed with two coexisting and typically unassociated X-linked conditions: he was initially diagnosed with X-linked agammaglobulinemia (XLA) followed by a diagnosis of X-linked chronic granulomatous disease (XCGD) and an as of yet unpublished hypomorphic gp91phox variant in the CYBB gene. […] X-linked agammaglobulinemia (XLA) and X-linked chronic granulomatous disease (XCGD) are two of the five most common X-linked immunodeficiencies, both often diagnosed via single- or multi-gene Sanger sequencing despite the rapidly increasing use of next-generation sequencing. […] XLA is an antibody deficiency syndrome caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to deficiency of mature B lymphocytes, agammaglobulinemia, and susceptibility to infection.

• #1 Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

  https://www.mdpi.com/2227-9059/11/3/959

  XLA, in the past, thought easily managed and complications avoided with rapid initiation of immunoglobulin replacement, now has a known association with autoimmunity/inflammatory conditions, including diarrhea and IBD-like enteropathy. […] This case brings up thought-provoking questions about a possible mechanism for co-occurring XLA and X-CGD, which requires further study, and the development of new treatment strategies for patients with inborn errors of immunity (IEI).

• #1 Mycoplasma pneumonia in a patient with X-linked agammaglobulinemia | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09743-w

  Mycoplasma pneumoniae, a prominent etiological cause of community-acquired pneumonia, particularly affects children with immunodeficiency, often resulting in more severe illness. […] Following immunoglobulin treatment, the patients condition gradually improved. However, given the chronic nature of XLA, lifelong administration of immunoglobulins and additional interventions to manage infections or other complications are likely necessary. Regular monitoring and provision of supportive care are essential for optimal management of XLA. […] Atypical XLA patients are often initially misdiagnosed with other diseases, such as common variable immunodeficiency, chronic respiratory infections, autoimmune diseases, and so on. Clinical differentiation from these common diseases can be challenging, complicating the treatment process.

• #1 Mycoplasma pneumonia in a patient with X-linked agammaglobulinemia | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09743-w

  Hence, monitoring the biological trough concentration of the drug is pivotal in evaluating both efficacy and safety of the treatment regimen. Documenting longitudinal changes in clinical symptoms and serum IgG levels on a personalized basis is anticipated to augment patient care. […] As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. By identifying the specific gene mutations responsible for XLA, healthcare professionals can provide targeted treatments and interventions to manage the condition effectively. […] In conclusion, the prognosis for patients with XLA can be favorably impacted through prompt diagnosis and the judicious use of immunoglobulin therapy.

• #2 X-linked agammaglobulinemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/x-linked-agammaglobulinemia/symptoms-causes/syc-20361635

  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. […] Most babies with XLA appear healthy for the first few months. They’re protected by the proteins called antibodies they got from their mothers before birth. […] When these antibodies leave their systems, the babies begin to get repeat bacterial infections. The infections can be life-threatening. Infections might involve the ears, lungs, sinuses and skin. […] Male infants born with XLA have very small tonsils and small or no lymph nodes. […] People with XLA can live mostly typical lives. They should try to take part in regular activities for their ages. But repeat infections linked to XLA will likely need careful watching and treatment. They can damage organs and be life-threatening.

• #2 X-Linked Agammaglobulinemia – Immune Disorders – Merck Manual Consumer Version

  https://www.merckmanuals.com/home/immune-disorders/immunodeficiency-disorders/x-linked-agammaglobulinemia

  Infants with X-linked agammaglobulinemia start having recurring coughs and/or infections of the nose, ears, skin, sinuses, and lungs at about age 6 months. […] At about age 6 months, levels of these immunoglobulins start to decrease, and affected infants start having recurring cough, nasal infections (rhinitis), and/or infections of the ears, skin, sinuses, and lungs. The infections are usually due to bacteria such as pneumococci, streptococci, and Haemophilus bacteria. Some unusual viral infections of the brain may develop. […] X-linked agammaglobulinemia increases the risk of developing infections in the joints (infectious arthritis), irreversible widening due to chronic inflammation of the airways (bronchiectasis), and certain cancers. […] With early diagnosis and treatment, life span is often unaffected, unless brain infections develop.

• #2 X-Linked Agammaglobulinemia

  https://www.aaaai.org/conditions-treatments/primary-immunodeficiency-disease/x-linked-agammaglobulinemia

  X-Linked agammaglobulinemia (XLA) is an inherited immunodeficiency in which the body is unable to produce the antibodies needed to defend against bacteria and viruses. […] XLA often becomes apparent in infancy due to recurrent and severe bacterial infections including: Ear infections, Sinusitis, Pneumonia, Diarrhea due to a parasite called Giardia. […] When affected by XLA, the infant cannot do this on his own, and becomes susceptible to these recurrent infections.

• #2 X-Linked (Bruton) Agammaglobulinemia: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1050956-overview

  X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is an inherited immunodeficiency disease caused by mutations in the gene coding for Bruton tyrosine kinase (BTK). […] Without mature B lymphocytes, antibody-producing plasma cells are also absent. […] The spleen, the tonsils, the adenoids, the Peyer patches in the intestines, and the peripheral lymph nodes may all be reduced in size or absent in individuals with X-linked agammaglobulinemia (XLA). […] Males with XLA have a total or almost total absence of B lymphocytes and plasma cells. […] Infections begin once transferred maternal immunoglobulin G (IgG) antibodies have been catabolized, typically at about 6 months of age. […] Children typically clinically manifest the disease at age 3-9 months with pneumonia, otitis media, cellulitis, meningitis, osteomyelitis, diarrhea, or sepsis.

• #2 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  Individuals with any form of antibody deficiency with absent B cells are prone to develop infections. […] The deficiency of antibody production is present at birth, and infections may begin at any age. […] On physical examination, most individuals with agammaglobulinemia have very small tonsils and lymph nodes, which are the glands in the neck. […] 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. […] The first screening test should be an evaluation of serum immunoglobulins. […] A low percentage of B cells (1% or less of the lymphocytes) in the blood is the most characteristic and reliable laboratory finding in someone with agammaglobulinemia.

• #2 X-Linked Agammaglobulinemia – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/x-linked-agammaglobulinemia/?utm_source=pubmedlink&utm_campaign=MDS&utm_content=31430

  X-linked agammaglobulinemia or XLA is a frequent immune system disorder in children that stops them from creating antibodies, which are proteins that help fight off infections. […] This absence of antibodies makes people with XLA highly susceptible to certain bacterial infections, viruses, and chronic diarrhea caused by a parasite named Giardia lamblia. […] People with XLA usually start experiencing recurring respiratory infections like sinusitis and middle ear infections after 6 to 9 months of age, when the protective maternal antibodies naturally disappear. The disorder is often suspected when the person needs hospitalization and intravenous antibiotics to treat bacterial pneumonia. […] Despite the lack of a cure for XLA, early treatment with immunoglobulin and antibiotics can prevent and manage infections.

• #2 X-linked Agammaglobulinemia (xla)

  https://www.pediatriconcall.com/articles/immunodeficiencies/x-linked-agammaglobulinemia-xla/x-linked-agammaglobulinemia-xla-patient-education

  Symptoms of XLA are recurrent bacterial infections, especially in the ears, sinuses, and lungs. They may also get diarrhea, skin infections, and serious infections such as septicemia. Common organisms causing infections in these patients are Pneumococcus, Streptococcus, Staphylococcus, and Haemophilus influenza. […] Most XLA patients who receive immunoglobulins will be able to lead a relatively normal life.

• #2 X-Linked (Bruton) Agammaglobulinemia Clinical Presentation: History, Physical Examination, Complications

  https://emedicine.medscape.com/article/1050956-clinical

  Individuals who are affected may have an increased incidence of autoimmune diseases leading to thrombocytopenia, neutropenia, hemolytic anemia, and rheumatoid arthritis. […] Persistent enteroviral infections may rarely lead to fatal encephalitis or a dermatomyositis-meningoencephalitis syndrome. […] Males affected with XLA usually present when they are younger than 1 year with unusually severe and/or recurrent otitis media, sinopulmonary infections, and pneumonia. […] For children younger than 12 years, typical infections are caused by encapsulated bacteria. […] In adulthood, skin manifestations become more common, usually due to Staphylococcus and group A Streptococcus organisms. […] Both infants and adults can have autoimmune diseases associated with XLA. […] Diarrhea is common and is caused by Giardia or Campylobacter species. […] Patients with XLA are prone to enteroviral infections, including poliovirus. […] Complications for patients with XLA include chronic sinopulmonary infections, enteroviral infections of the central nervous system, increased occurrence of autoimmune diseases, and skin infections.

• #2

  https://link.springer.com/article/10.1007/s10875-023-01502-x

  To understand the natural history and clinical outcomes for patients with X-linked agammaglobulinemia (XLA) in the United States utilizing the United States Immunodeficiency Network (USIDNET) patient registry. […] The respiratory tract was the most affected organ system (51.2% of patients) followed by gastrointestinal (40%), neurological (35.4%), and musculoskeletal (28.3%). Infections were common both before and after diagnosis, despite IgGR therapy. […] Current therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function. […] Neurologic condition was the most common underlying co-morbidity for those XLA patients who died. […] Symptoms of allergic disease such as chronic rhinitis, eczema/atopic dermatitis, and urticaria were reported in 28% of patients.

• #2 X-Linked (Bruton) Agammaglobulinemia Clinical Presentation: History, Physical Examination, Complications

  https://emedicine.medscape.com/article/1050956-clinical

  Recurrent infections begin in infancy and persist throughout adulthood. […] The most common presentation of X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is increased susceptibility to encapsulated pyogenic bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas species. […] Skin infections in patients with XLA are mostly caused by group A streptococci and Staphylococcus aureus, and they can present as impetigo, cellulitis, abscesses, or furuncles. […] A form of eczema that resembles atopic dermatitis may be evident, along with an increased incidence of pyoderma gangrenosum, vitiligo, alopecia totalis, and Stevens-Johnson syndrome (from increased use of medications). […] Other infections that commonly present with XLA include enteroviral infections, sepsis, meningitis, and bacterial diarrhea (often caused by common organisms, such as Campylobacter jejuni and Giardia species).

• #2 X-linked Agammaglobulinemia (Congenital Agammaglobulinemia, Bruton’s Agammaglobulinemia – Dermatology Advisor

  https://www.dermatologyadvisor.com/home/decision-support-in-medicine/dermatology/x-linked-agammaglobulinemia-congenital-agammaglobulinemia-brutons-agammaglobulinemia/

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by an intrinsic defect in the maturation of pre-B-cells to B-cells and ultimately immunoglobulin-secreting plasma cells. As a result, affected patients (male) have markedly reduced serum immunoglobulin levels and nearly absent antibody levels. […] An increased susceptibility to infection is the clinical hallmark of the disorder. Recurrent pyogenic infections such as otitis, pneumonia, bacteremia/sepsis, meningitis, osteomyelitis/septic arthritis and skin infections are common and are usually caused by encapsulated bacteria such as Pneumococcus, streptococcus, Haemophilus influenzae, and Pseudomonas. […] The complications of XLA are related to the increased susceptibility to infection. If the diagnosis is not made early in life and treatment not initiated before complications of the infections develop, patients may suffer with chronic pulmonary infections and pulmonary insufficiency. Similarly, central nervous system infections, such as meningitis, may lead to neurologic sequelae and developmental issues. Finally, hearing loss secondary to chronic otitis media was relatively common in the first few decades after discovery of the disease, although less common now.

• #2 Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-clinical-genetic-profiles-patients-with-S0301054618300740

  Three patients suffered from severe infections, such as osteomyelitis (P7), infective endocarditis (P1) and encephalitis (P12). […] Our results suggest that the correlation between the specific mutation in BTK and the severity of the disease alone may not be sufficient to predict clinical progress in a patient with XLA based on the mutation. […] Infection is the initial manifestation of XLA patients. […] Our results also suggest that the development of arthritis might be due to exaggerated inflammatory responses to circulating microbial products. […] X-linked agammaglobulinemia might be associated with some autoimmune diseases. […] In conclusion, we have identified our mutation profile to be different from those in the rest of the world.

• #2 X-linked Agammaglobulinemia: diagnosis story

  https://3billion.io/blog/x-linked-agammaglobulinemia-diagnosis-story

  During this period, his lung function worsened as a result of bronchiectasis, in which his airway walls became irreversibly thickened, damaged, and scarred. He also had arthritis of both small and large joints and recurrent abdominal pain with diarrhea needing anti-diarrhea (loperamide three times/week). […] To make matters worse, he started to have palpitations with difficulty to breath around the young age of 31 years old. He was referred to the National Heart Centre and was diagnosed with chronic rheumatic heart disease. A year after diagnosis, he had to undergo heart surgery to replace one of his damaged heart valves. […] Upon clinical examination, Saravanan was a thin man with slight, rapid breathing. There were signs of chronic lung disease indicated by grade 4 finger clubbing and chest wall deformities. He had absent tonsils, a mildly enlarged liver, and an audible click on heart examination. Investigations done in our center revealed absent B cells and low levels of antibodies (IgA, IgM and IgE). Antibody IgG was highly probable because he had just received IVIG treatment a few days prior. […] After a long 24 years of waiting, the definitive diagnosis of X-linked agammaglobulinaemia (XLA) was established via genetic testing whereby a mutation in the BTK gene was found.

• #2 Mortality and morbidity in patients with X-linked agammaglobulinaemia | Allergologia et Immunopathologia

  https://www.elsevier.es/en-revista-allergologia-et-immunopathologia-105-articulo-mortality-morbidity-in-patients-with-S0301054613002863

  X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. […] Among 41 patients, 26.8% died during the follow up period. […] The most common first presentation was pneumonia in 10 patients, chronic otitis media in seven (17.0%), and diarrhoea in five (12.1%). […] The main cause of mortality in our patients was respiratory failure due to the chronic respiratory infections which suggests that, despite appropriate serum IgG level of patients during follow-up period, chronic lung disease (CLD) remains the most dangerous complication in XLA patients.

• #2 X-linked agammaglobulinemia | Children’s Wisconsin

  https://childrenswi.org/medical-care/immune-deficiency/immune-disorders/x-linked-agammaglobulinemia

  The symptoms of X-linked agammaglobulinemia usually become apparent in the first 6 to 9 months of age, but can present as late as 3 to 5 years of age. The following are the most common symptoms of X-linked agammaglobulinemia. However, each child may experience symptoms differently. Symptoms may include: […] numerous, serious, and/or life-threatening illnesses, including, but not limited to the following: […] Cancers including leukemia, lymphoma, and colon cancer, have been reported in a small percentage of older patients with X-linked agammaglobulinemia. […] The symptoms of X-linked agammaglobulinemia may resemble other problems or medical conditions. Always consult your child’s physician for a diagnosis. […] Without antibody replacement, these children could die at an early age from severe infections. Children who develop chronic lung disease with bronchiectasis (widening and scarring of the airways) may have a shortened lifespan, in some cases. However, those children with X-linked agammaglobulinemia who are diagnosed and treated early should be able to lead normal, active lives.

• #2 X-Linked Agammaglobulinemia | Loma Linda University Children’s Health

  https://lluch.org/conditions/x-linked-agammaglobulinemia

  X-linked agammaglobulinemia is a rare genetic disease. It causes a weakened immune system. […] A child with this disease cant make antibodies that are part of gamma globulins in blood plasma. Antibodies are the body’s main defense against germs like bacteria and viruses. So a child with this disease cant fight off infections caused by bacteria and some viruses. […] Boys with this disease are more likely to get infections in the middle ear, sinuses, and lungs. The infections can also involve the bloodstream or internal organs. Most children with this disease who are treated early can lead normal, active lives. […] The symptoms of this disease usually show up in the first 6 to 9 months of age. But they can also show up as late as age 3 to 5 years. […] Common symptoms include: Many serious or life-threatening illnesses, such as infections of the nasal passages, skin, eyes, bones, lungs, digestive tract, and bloodstream, Failure to grow, No tonsils or adenoids, Joint disease, mainly in the knees, similar to juvenile rheumatoid arthritis, Breakdown of red blood cells (autoimmune hemolytic anemia), Kidney inflammation (glomerulonephritis), Fewer white blood cells called neutrophils (neutropenia), Skin and muscle inflammation (dermatomyositis).

• #2 X-linked agammaglobulinemia (XLA) – Children’s Health Immunology

  https://www.childrens.com/specialties-services/conditions/xla

  X-linked agammaglobulinemia (XLA) is an inherited (congenital) immunodeficiency disease in which the body is unable to produce antibodies needed to defend against pathogens (bacteria, viruses, fungi). […] Your doctor may suspect XLA if your infant experiences severe and recurrent bacterial infections, including: Ear infections, Sinusitis, Pneumonia, Diarrhea from the parasite Giardia. […] Infections of the membranes that cover the brain (meningitis) or infections that affect the brain (encephalitis) can occur in children with XLA (and girls with agammaglobulinemia) even when they are being treated with immunoglobulin therapy. […] If your child has these signs, as well as a history of severe bacterial infections, the doctor will order a blood test to evaluate serum immunoglobulins (antibodies). In most children with XLA, all antibody levels are low or absent.

• #2 X-Linked Agammaglobulinemia – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/x-linked-agammaglobulinemia/

  Before the use of regular immunoglobulin replacement therapy, most children with XLA a condition that severely weakens the immune system passed away before reaching only 10 years old. These deaths were usually due to complications from lung disease, severe widespread infections known as sepsis, or meningitis, which is an infection that inflames the brain and spinal cord membranes. […] Despite chronic lung disease continuing to be a serious concern, patients with XLA now often live into adulthood, thanks to improvements in medical treatment practices. If diagnosed early, namely before the age of five, these individuals can have a far better prognosis. By receiving regular immunoglobulin replacement therapy a treatment that boosts the immune system and taking prescribed antibiotics to treat or prevent infections, affected individuals can anticipate a normal quality of life and a life expectancy beyond the age of 40.

• #2

  https://link.springer.com/article/10.1007/s12016-021-08870-5

  Interruptions or alterations in the B cell development pathway can lead to primary B cell immunodeficiency with resultant absence or diminished immunoglobulin production. While the most common cause of congenital agammaglobulinemia is X-linked agammaglobulinemia (XLA), accounting for approximately 85% of cases, other genetic forms of agammaglobulinemia have been identified. […] The diagnosis of XLA is often delayed, and can be missed if patient has a mild phenotype. The lack of correlation between phenotype and genotype in this condition makes management and predicting outcomes quite difficult. […] In contrast, while less common, autosomal recessive forms of agammaglobulinemia present at younger ages and with typically more severe clinical features resulting in an earlier diagnosis. Some diagnostic innovations, such as KREC level measurements and serum BCMA measurements, may aid in facilitating an earlier identification of agammaglobulinemia leading to prompt treatment. Earlier diagnosis may improve the overall health of patients with XLA.

• #2 Mycoplasma pneumonia in a patient with X-linked agammaglobulinemia | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09743-w

  Mycoplasma pneumoniae, a prominent etiological cause of community-acquired pneumonia, particularly affects children with immunodeficiency, often resulting in more severe illness. […] Following immunoglobulin treatment, the patients condition gradually improved. However, given the chronic nature of XLA, lifelong administration of immunoglobulins and additional interventions to manage infections or other complications are likely necessary. Regular monitoring and provision of supportive care are essential for optimal management of XLA. […] Atypical XLA patients are often initially misdiagnosed with other diseases, such as common variable immunodeficiency, chronic respiratory infections, autoimmune diseases, and so on. Clinical differentiation from these common diseases can be challenging, complicating the treatment process.

• #2 Azthena logo with the word Azthena

  https://www.news-medical.net/health/What-is-Agammaglobulinemia.aspx

  Serial bacterial infections are the main symptoms of agammaglobulinemia, which are caused by deficiencies in certain immunological responses caused by abnormalities in B-lymphocytes. Infections commonly occur in the gastrointestinal tract, lungs, skin, joints, and upper respiratory tracts. […] Recurrent, pyogenic bacterial infections in young boys and a near-complete absence of all immunoglobulin isotypes are among the clinical manifestations of XLA. […] Prior to diagnosis, recurrent otitis is the most frequent infection. In addition, conjunctivitis, sinopulmonary infections, diarrhea, and skin infections are common. […] When people with XLA acquire a serious, life-threatening condition such as pneumonia, empyema, meningitis, sepsis, or septic arthritis, they are diagnosed with immunodeficiency. Neutropenia has been identified as a prevalent XLA symptom. […] The prognosis for people with XLA has improved dramatically in the last 25 years as a result of earlier diagnosis, the discovery of gammaglobulin preparations that allow for normal blood IgG concentrations, and more liberal antibiotic use.

• #2

  https://link.springer.com/article/10.1007/s10875-023-01502-x

  In this cohort, 222 patients (92.5%) reported infections, with 1054 total infections reported in the Registry. […] After diagnosis, 178 patients reported any medical condition: 89 patients (50%) reported four or more conditions, 40 (22%) reported 1 condition, 28 (15.7%) reported two conditions, and 21 (11.8%) reported 3 conditions. […] The most common underlying co-morbid conditions in these deceased patients were neurologic (75%), followed by respiratory (70%). […] Mortality in the past 20 years appears improved among this US cohort, with only one death since 2000.

• #2 X-Linked Agammaglobulinemia: Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/24955-x-linked-agammaglobulinemia

  People with X-linked agammaglobulinemia usually have small or missing lymph nodes, tonsils and adenoids due to their underdeveloped immune systems. They experience frequent bacterial infections in childhood, including: […] Changes in your BTK gene mean you cant fight off illness the same way someone without the mutation can. This means you get sick frequently, sometimes with life-threatening illnesses. […] People with XLA need treatment for the rest of their lives so theyre less vulnerable to illness. Theyll need to work closely with their healthcare provider to treat any illnesses as soon as possible. You or your child can expect to miss more days of school and work due to illness than others. […] Thanks to advances in treatment, people with XLA live into adulthood in developed countries like the U.S. In still-developing countries, getting a diagnosis and treatment is much harder. This usually means children with XLA dont live as long.

• #2 X-linked agammaglobulinemia // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/x-linked-agammaglobulinemia

  Most babies with XLA appear healthy for the first few months. When these antibodies leave their systems, the babies begin to get repeat bacterial infections. The infections can be life-threatening. Infections might involve the ears, lungs, sinuses and skin. Male infants born with XLA have: Very small tonsils. Small or no lymph nodes. […] People with XLA can live mostly typical lives. They should try to take part in regular activities for their ages. But repeat infections linked to XLA will likely need careful watching and treatment. They can damage organs and be life-threatening.

• #2 Agammaglobulinemia: X-linked (XLA) and autosomal recessive (ARA) | Immune Deficiency Foundation

  https://primaryimmune.org/understanding-primary-immunodeficiency/types-of-pi/agammaglobulinemia-x-linked-and-autosomal

  The diagnosis of XLA can be confirmed by demonstrating the absence of BTK protein in monocytes or platelets or by the detection of a variant in the BTK gene. […] At this time, the only treatment for individuals with agammaglobulinemia is immunoglobulin (Ig) replacement therapy. […] Ig replacement therapy for those with agammaglobulinemia replenishes some of the antibodies that they are lacking. […] People with antibody deficiency with absent B cells should not receive any live viral vaccines, such as live polio, the measles, mumps, rubella (MMR) vaccine, the chicken pox vaccine, the rotavirus vaccine, yellow fever, live typhoid, or the live shingles vaccine. […] Most individuals with antibody deficiency with absent B cells, who receive Ig replacement therapy on a regular basis, will be able to lead relatively normal lives.

• #2 X-linked agammaglobulinemia (XLA) – Children’s Health Immunology

  https://www.childrens.com/specialties-services/conditions/xla

  If your child is diagnosed with XLA, they will be treated with immunoglobulin IgG (antibodies) therapy on a regular basis for the rest of his life. IgG therapy can be given through a catheter in your child’s vein (intravenous; IVIG) or subcutaneously (SCIG). The decision to use one or the other depends on what’s best for your child and your family. There is currently no cure for XLA. […] Most individuals with XLA who receive immunoglobulin on a regular basis can lead normal, healthy lives.

• #2 Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

  https://www.mdpi.com/2227-9059/11/3/959

  We present a unique and unusual case of a male patient diagnosed with two coexisting and typically unassociated X-linked conditions: he was initially diagnosed with X-linked agammaglobulinemia (XLA) followed by a diagnosis of X-linked chronic granulomatous disease (XCGD) and an as of yet unpublished hypomorphic gp91phox variant in the CYBB gene. […] X-linked agammaglobulinemia (XLA) and X-linked chronic granulomatous disease (XCGD) are two of the five most common X-linked immunodeficiencies, both often diagnosed via single- or multi-gene Sanger sequencing despite the rapidly increasing use of next-generation sequencing. […] XLA is an antibody deficiency syndrome caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to deficiency of mature B lymphocytes, agammaglobulinemia, and susceptibility to infection.

• #2 Bruton’s agammaglobulinemia in an adult male due to a novel mutation: a case report – Xu – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/10008/html

  X-linked agammaglobulinemia (XLA) is caused by mutation in the gene coding for Brutons tyrosine kinase (BTK), which impairs peripheral B cell maturation and hypogammaglobulinemia. The patient had a history of recurrent respiratory tract infection which eventually progressed to chronic type II respiratory failure. Patients with XLA are particularly susceptible to respiratory infections. In our patient, Lower respiratory tract secretion specimens were obtained on bronchoscopy at the time of endotracheal intubation for respiratory failure. BTK mutations lead to impaired humoral immunity, thus rendering the patient susceptible to Streptococci, Neisseria, Enterovirus and other pathogens. The patient had a B (CD19+, CD20+) lymphocyte count of nearly 0% and low levels of IgG, IgM and IgA. This case highlights the need for a high degree of suspicion for XLA on the part of clinicians to avoid missed diagnosis.

• #2 X-linked agammaglobulinemia diagnosed late in life: case report and review of the literature | Clinical and Molecular Allergy | Full Text

  https://clinicalmolecularallergy.biomedcentral.com/articles/10.1186/1476-7961-6-5

  These findings along with poor specific antibody responses to pneumococcal antigens lead to genetic mutational analysis for Btk mutations. Both patients were found to have hemizygous Btk mutations, in the absence of mutations described with CVID (such as TACI gene mutations). […] Any male patient who presents with recurrent infections, hypogammaglobulinemia, and low to absent CD19+ B cells should be suspected of having XLA. In atypical cases such as these two that we present, the virtual absence of CD19+ B cells may be a sensitive test to differentiate XLA from CVID, which may lead to the more specific genetic mutational analysis for Btk mutations.

• #2 Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

  https://www.mdpi.com/2227-9059/11/3/959

  Immunoglobulin replacement continues to be the cornerstone of treatment, with improved outcomes in cases of early diagnosis and treatment initiation. […] A Caucasian boy presented at 24 months of age with a history of recurrent sinopulmonary infections and croup. […] On laboratory evaluation, he had undetectable serum IgG, IgA, and IgE; low IgM, and <1% circulating CD19+ B cells, raising suspicion for XLA or an alternative early defect in the development of B-cells. [...] He started intravenous immunoglobulin replacement (IVIG) at 0.5 g/kg every 4 weeks with adjustments to achieve infection control. [...] Within the first three years following diagnosis, the patient’s infection frequency improved on IVIG despite intermittent breakthrough infections with sinusitis in the winter months and a single episode of otitis media.

• #2 Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

  https://www.mdpi.com/2227-9059/11/3/959

  At 6 years of age, he developed painful gingivitis. […] The inflamed gingival tissue was biopsied and cauterized by the patient’s oral surgeon. […] Histopathological analyses of the tissue revealed “mucosal ulceration with focal granulomatous inflammation, hyperparakeratosis and acanthosis”, consistent with granulomatosis gingivitis. […] Due to the pathology revealing granulomas, functional testing by flow cytometry was completed for chronic granulomatous disease and showed a reduced but not absent neutrophil oxidative burst. […] The patient started daily Trimethoprim/Sulfamethoxazole prophylaxis while maternal testing was completed to determine the inheritance pattern prior to genetic testing. […] Following confirmation of a second genetic diagnosis (XCGD) in the patient, he developed gastrointestinal symptoms concerning Crohn’s disease or CGD colitis.

• #2 X-Linked Agammaglobulinemia – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/x-linked-agammaglobulinemia/?utm_source=pubmedlink&utm_campaign=MDS&utm_content=31430

  If XLA is suspected in infants or very young children, doctors will often ask the parents or caregivers about the child’s health history, including past and current illnesses, hospital stays, vaccinations, allergies, and medicines they have taken. […] If a patient often suffers from long-lasting or repeated infections such as conjunctivitis, respiratory tract infections, skin infections, ear infections, or diarrhea, this can signal XLA. […] Infants with XLA are typically born healthy, and outward symptoms may not appear until they are 6-8 months old. This is because, up until that point, they are still protected by their mothers antibodies. […] A physical exam will reveal that patients typically have underdeveloped (hypoplastic) lymphoid tissues. […] Lastly, the family’s medical history, including previous infections, hospital stays, surgeries, immunodeficiency diagnoses or symptoms, the health statuses of living relatives, and causes of death can also aid in diagnosing XLA.

• #2 Mycoplasma pneumonia in a patient with X-linked agammaglobulinemia | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09743-w

  Hence, monitoring the biological trough concentration of the drug is pivotal in evaluating both efficacy and safety of the treatment regimen. Documenting longitudinal changes in clinical symptoms and serum IgG levels on a personalized basis is anticipated to augment patient care. […] As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. By identifying the specific gene mutations responsible for XLA, healthcare professionals can provide targeted treatments and interventions to manage the condition effectively. […] In conclusion, the prognosis for patients with XLA can be favorably impacted through prompt diagnosis and the judicious use of immunoglobulin therapy.

• #2 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  There is currently no cure for XLA; however, early management with immunoglobulin replacement therapy and antibiotics 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 poses the danger of developing chronic, treatment-resistant infections, and end-organ damage that cannot be corrected. […] Complications associated with XLA usually arise from infections, especially those that have become recurrent. Susceptible individuals can become chronically ill and suffer organ damage. For example, repeated episodes of acute pneumonia may culminate in chronic lung disease and lead to bronchiectasis, which has the potential to reduce life expectancy. The likelihood that chronic infections will evolve into serious, life-threatening conditions increases with the length of delay in diagnosis. The later treatment begins, the more difficult it is to eradicate the causative organisms and prevent the systemic spread of infection to joints and vital organs.

• #3 X-Linked Agammaglobulinemia | Boston Children’s Hospital

  https://www.childrenshospital.org/conditions/x-linked-agammaglobulinemia

  Symptoms are likely to become apparent when your child is between 6 and 9 months old. Each child may experience symptoms differently, but common symptoms include an unusual susceptibility to numerous illnesses such as: […] The symptoms of X-linked agammaglobulinemia may resemble other problems or medical conditions. Always consult your child’s physician for a diagnosis. […] Children with X-linked agammaglobulinemia can become very ill or even die at an early age from severe infections. Children who develop chronic lung disease with bronchiectasis (widening and scarring of the airways) may have a shortened lifespan. But your child, if diagnosed and treated early, should be able to lead a relatively normal, active life, without the need for isolation.

• #3 X-Linked Agammaglobulinemia (XLA) – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/x-linked-agammaglobulinemia/

  Agammaglobulinemia is more commonly known as X-Linked agammaglobulinemia (XLA), Bruton’s agammaglobulinemia, or congenital agammaglobulinemia. It is a disorder caused by the body’s inability to produce B cells or immunoglobulins (antibodies) that the B cells make. When B Cells or immunoglobulin levels are below the normal range, it can cause recurrent infections (like the flu, strep throat, etc.), allergies, asthma, and a weakened immune system. The most commonly recognized clinical feature of agammaglobulinemia is recurrent infection. […] The symptoms of agammaglobulinemia appear at the age of 6 months when the placental immunoglobulins (IgG) run out. At the initial stages of life, the mother provides passive immunity to the fetus by transferring immunoglobulins through the placenta and protecting the newborn baby from various fatal infections.

• #3 X-linked Agammaglobulinemia (xla)

  https://www.pediatriconcall.com/articles/immunodeficiencies/x-linked-agammaglobulinemia-xla/x-linked-agammaglobulinemia-xla-patient-education

  Symptoms of XLA are recurrent bacterial infections, especially in the ears, sinuses, and lungs. They may also get diarrhea, skin infections, and serious infections such as septicemia. Common organisms causing infections in these patients are Pneumococcus, Streptococcus, Staphylococcus, and Haemophilus influenza. […] Most XLA patients who receive immunoglobulins will be able to lead a relatively normal life.

• #3 X-linked agammaglobulinemia | Children’s Wisconsin

  https://childrenswi.org/medical-care/immune-deficiency/immune-disorders/x-linked-agammaglobulinemia

  The symptoms of X-linked agammaglobulinemia usually become apparent in the first 6 to 9 months of age, but can present as late as 3 to 5 years of age. The following are the most common symptoms of X-linked agammaglobulinemia. However, each child may experience symptoms differently. Symptoms may include: […] numerous, serious, and/or life-threatening illnesses, including, but not limited to the following: […] Cancers including leukemia, lymphoma, and colon cancer, have been reported in a small percentage of older patients with X-linked agammaglobulinemia. […] The symptoms of X-linked agammaglobulinemia may resemble other problems or medical conditions. Always consult your child’s physician for a diagnosis. […] Without antibody replacement, these children could die at an early age from severe infections. Children who develop chronic lung disease with bronchiectasis (widening and scarring of the airways) may have a shortened lifespan, in some cases. However, those children with X-linked agammaglobulinemia who are diagnosed and treated early should be able to lead normal, active lives.

• #3 X-Linked Agammaglobulinemia in Children – Stanford Medicine Children’s Health

  https://www.stanfordchildrens.org/en/topic/default?id=x-linked-agammaglobulinemia-in-children-90-P01666

  X-linked agammaglobulinemia is a rare genetic disease. It causes a weakened immune system. A child with this disease cant make antibodies that are part of gamma globulins in blood plasma. So a child with this disease cant fight off infections caused by bacteria and by some viruses. Boys with this disease are more likely to get infections in the middle ear, sinuses, and lungs. The symptoms of this disease usually show up in the first 6 to 9 months of age. But they can also show up as late as age 3 to 5 years. Common symptoms include: Many serious or life-threatening illnesses such as infections of the nasal passages, skin, eyes, bones, lungs, digestive tract, and bloodstream […] Failure to grow […] No tonsils or adenoids […] Joint disease, mainly in the knees, similar to juvenile rheumatoid arthritis

• #3 Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-clinical-genetic-profiles-patients-with-S0301054618300740

  X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. […] The age of onset of the symptoms is usually after the 6th month of life which is in coincidence with the period where the maternal IgG fades. […] The patients suffer from recurrent bacterial infections associated with encapsulated, extracellular pyogenic pathogens such as Streptococcus pneumonae and Haemophilus influenzae. […] Clinical presentations of infection were identified in patients before XLA was diagnosed, all of those were upper respiratory tract infections. Lower tract infection was found in 19 cases (86.3%), whereas otitis media in 10 cases (45.5%) and chronic diarrhea in eight cases (36.4%).

• #3 Orphanet: X-linked agammaglobulinemia

  https://www.orpha.net/en/disease/detail/47

  A clinically variable form of isolated agammaglobulinemia, an inherited immunodeficiency disorder, characterized in affected males by recurrent bacterial infections during infancy. […] Affected individuals are usually healthy in the first few months of life due to residual maternal immunoglobulins. The majority of patients develop recurrent or persistent bacterial infections, most commonly caused by S. pneumoniae and H. influenzae, within the first two years of life: otitis media, conjunctivitis, sinusitis, respiratory infections, diarrhea and skin infections (impetigo, cellulitis, abscesses, and furuncles). Other severe infections may include empyema, meningitis, sepsis, or septic arthritis. Pyoderma or cellulitis (associated with neutropenia) and pseudomonas or staphylococcal sepsis are frequent presenting findings, particularly in patients less than 12 months of age.

• #3 X-Linked Agammaglobulinemia | Loma Linda University Children’s Health

  https://lluch.org/conditions/x-linked-agammaglobulinemia

  X-linked agammaglobulinemia is a rare genetic disease. It causes a weakened immune system. […] A child with this disease cant make antibodies that are part of gamma globulins in blood plasma. Antibodies are the body’s main defense against germs like bacteria and viruses. So a child with this disease cant fight off infections caused by bacteria and some viruses. […] Boys with this disease are more likely to get infections in the middle ear, sinuses, and lungs. The infections can also involve the bloodstream or internal organs. Most children with this disease who are treated early can lead normal, active lives. […] The symptoms of this disease usually show up in the first 6 to 9 months of age. But they can also show up as late as age 3 to 5 years. […] Common symptoms include: Many serious or life-threatening illnesses, such as infections of the nasal passages, skin, eyes, bones, lungs, digestive tract, and bloodstream, Failure to grow, No tonsils or adenoids, Joint disease, mainly in the knees, similar to juvenile rheumatoid arthritis, Breakdown of red blood cells (autoimmune hemolytic anemia), Kidney inflammation (glomerulonephritis), Fewer white blood cells called neutrophils (neutropenia), Skin and muscle inflammation (dermatomyositis).

• #3 X-linked Agammaglobulinemia: diagnosis story

  https://3billion.io/blog/x-linked-agammaglobulinemia-diagnosis-story

  Saravanan was born to an Indian couple with no history of consanguinity. As far as he can remember, he was a healthy happy child until the age of 2 years. It was then that marked a life changing event whereby his left eye had to be enucleated due to severe infection. Following the devastating event, he had frequent episodes of ear infections, sinus infections, recurrent fever, and abdominal bloating which required multiple clinic visits, and luckily were resolved with symptomatic treatment. […] It was in the year 1997 when he was 16 years old, he had an episode of severe lung infection that had him admitted for 20 days. Initial blood tests showed he had low antibodies. Unfortunately, no further investigations were performed, and he was not properly followed up. He was started on antibody treatment at only the age of 17 years. This treatment known as intravenous immunoglobulin (IVIG), was given at a frequency of 4 times a week for one year, but was forced to stop due to financial difficulties.

• #3 X-linked Agammaglobulinemia: diagnosis story

  https://3billion.io/blog/x-linked-agammaglobulinemia-diagnosis-story

  During this period, his lung function worsened as a result of bronchiectasis, in which his airway walls became irreversibly thickened, damaged, and scarred. He also had arthritis of both small and large joints and recurrent abdominal pain with diarrhea needing anti-diarrhea (loperamide three times/week). […] To make matters worse, he started to have palpitations with difficulty to breath around the young age of 31 years old. He was referred to the National Heart Centre and was diagnosed with chronic rheumatic heart disease. A year after diagnosis, he had to undergo heart surgery to replace one of his damaged heart valves. […] Upon clinical examination, Saravanan was a thin man with slight, rapid breathing. There were signs of chronic lung disease indicated by grade 4 finger clubbing and chest wall deformities. He had absent tonsils, a mildly enlarged liver, and an audible click on heart examination. Investigations done in our center revealed absent B cells and low levels of antibodies (IgA, IgM and IgE). Antibody IgG was highly probable because he had just received IVIG treatment a few days prior. […] After a long 24 years of waiting, the definitive diagnosis of X-linked agammaglobulinaemia (XLA) was established via genetic testing whereby a mutation in the BTK gene was found.

• #3 X-Linked Agammaglobulinemia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK549865/

  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 important factor in the mortality in patients with XLA, life expectancy extends into adulthood. Affected individuals who get diagnosed early (i.e., before five years of age) receive regular immunoglobulin replacement therapy and are prescribed antibiotics to treat or prevent infections can be expected to have a normal quality of life and live beyond the age of 40.

• #3 Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene | Allergologia et Immunopathologia

  https://www.elsevier.es/es-revista-allergologia-et-immunopathologia-105-articulo-clinical-genetic-profiles-patients-with-S0301054618300740

  Three patients suffered from severe infections, such as osteomyelitis (P7), infective endocarditis (P1) and encephalitis (P12). […] Our results suggest that the correlation between the specific mutation in BTK and the severity of the disease alone may not be sufficient to predict clinical progress in a patient with XLA based on the mutation. […] Infection is the initial manifestation of XLA patients. […] Our results also suggest that the development of arthritis might be due to exaggerated inflammatory responses to circulating microbial products. […] X-linked agammaglobulinemia might be associated with some autoimmune diseases. […] In conclusion, we have identified our mutation profile to be different from those in the rest of the world.

• #3 X-Linked Agammaglobulinemia in Children

  http://library.oumedicine.com/Conditions/COPD/Tools/90,P01666

  Failure to grow […] No tonsils or adenoids […] Joint disease, mainly in the knees, similar to juvenile rheumatoid arthritis […] Breakdown of red blood cells (autoimmune hemolytic anemia) […] Kidney inflammation (glomerulonephritis) […] Fewer white blood cells called neutrophils (neutropenia) […] Skin and muscle inflammation (dermatomyositis) […] A few older children with this disease may have cancers such as leukemia, lymphoma, or colon cancer. […] Without antibody replacement, a child with this disease could die at an early age from severe infections. Some children who get chronic lung disease with widening and scarring of the airways (bronchiectasis) may have a shortened lifespan. But most children with X-linked agammaglobulinemia who are treated early can lead normal, active lives.

• #3 X-LINKED (BRUTON) AGAMMAGLOBULINEMIA (XLA)

  https://medicover-genetics.com/product/x-linked-agammaglobulinemia-xla/

  X-linked agammaglobulinemia (XLA), also called Bruton agammaglobulinemia, (incidence approximately 1:100,000) is a primary humoral immunodeficiency syndrome based on a B cell maturation disturbance. The clinical symptoms begin between the 4th and 12th month of life with severe bacterial infections (such as otitis media, pneumonia, meningitis and sepsis) caused especially by encapsulated bacteria. One of the most common infections is chronic sinusitis. Although the defense against viral infections is generally not impaired, patients are susceptible to enterovirus infections. Some of those affected develop chronic infections such as dermatomyositis or meningoencephalitis, and about 20% develop arthritis. […] The B cell maturation disturbance shows itself through massively reduced B cell counts and an almost complete absence of plasma cells and immunoglobulins of all isotypes. T lymphocyte numbers and functions are normal. Despite the frequent infections, small or missing tonsils, adenoids, and lymph nodes are noticed during clinical examination. The therapy consists of the administration of immunoglobulins and antibiotics according to the pathogen. Complications include chronic lung disease and an increased risk of colon cancer and lymphoreticular malignancies.

• #3 Mycoplasma pneumonia in a patient with X-linked agammaglobulinemia | BMC Infectious Diseases | Full Text

  https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09743-w

  Hence, monitoring the biological trough concentration of the drug is pivotal in evaluating both efficacy and safety of the treatment regimen. Documenting longitudinal changes in clinical symptoms and serum IgG levels on a personalized basis is anticipated to augment patient care. […] As patients with XLA have complete immunoglobulin defects and develop severe and recurrent infections, early diagnosis would be beneficial for the improvement of their quality of life. By identifying the specific gene mutations responsible for XLA, healthcare professionals can provide targeted treatments and interventions to manage the condition effectively. […] In conclusion, the prognosis for patients with XLA can be favorably impacted through prompt diagnosis and the judicious use of immunoglobulin therapy.

• #3 X-Linked Agammaglobulinemia – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/x-linked-agammaglobulinemia/

  Before the use of regular immunoglobulin replacement therapy, most children with XLA a condition that severely weakens the immune system passed away before reaching only 10 years old. These deaths were usually due to complications from lung disease, severe widespread infections known as sepsis, or meningitis, which is an infection that inflames the brain and spinal cord membranes. […] Despite chronic lung disease continuing to be a serious concern, patients with XLA now often live into adulthood, thanks to improvements in medical treatment practices. If diagnosed early, namely before the age of five, these individuals can have a far better prognosis. By receiving regular immunoglobulin replacement therapy a treatment that boosts the immune system and taking prescribed antibiotics to treat or prevent infections, affected individuals can anticipate a normal quality of life and a life expectancy beyond the age of 40.

• #3 X-Linked Agammaglobulinemia (XLA) – AmeriPharma® Specialty Care

  https://ameripharmaspecialty.com/other-health-conditions/x-linked-agammaglobulinemia/

  Individuals with agammaglobulinemia show growth retardation because of frequent and repetitive bacterial or viral infections. […] XLA could be fatal if left untreated, and there are higher possibilities that an individual with XLA may experience severe life-threatening infections and a low survival rate. […] The life expectancy of patients with agammaglobulinemia can be reduced due to recurrent bacterial or viral infections. Those who get many severe infections will have a worse outlook than those who don’t get as many infections. […] However, most individuals with XLA who get immunoglobulin regularly will be able to live everyday lives. Catching this condition early and getting on antibiotics or immunoglobulin treatment can limit infections, prevent complications, and improve life expectancy.

• #3 X-Linked Aagammaglobulinemia: Causes, Symptoms, and Treatments | SELF

  https://www.self.com/story/understanding-x-linked-agammaglobulinemia

  X-linked agammaglobulinemia (a-gam-uh-glob-u-lih-NEE-me-uh) also called XLA is an inherited (genetic) immune system disorder that reduces your ability to fight infections. People with XLA might get infections of the inner ear, sinuses, respiratory tract, bloodstream, and internal organs. […] Most people with XLA are diagnosed in infancy or early childhood, after they’ve had repeated infections. Some people aren’t diagnosed until adulthood. […] Babies with XLA generally appear healthy during their first couple months because they’re protected by the antibodies they got from their mothers before birth. When these antibodies clear from their systems, the babies begin to develop often severe, recurrent bacterial infections such as of the ears, lungs, sinuses, and skin that can be life-threatening. […] Male infants born with XLA have very small tonsils and small or no lymph nodes. […] However, recurrent infections related to XLA will likely require careful attention and aggressive treatment. They can cause organ damage and be life-threatening.

• #3 X-linked agammaglobulinemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/x-linked-agammaglobulinemia/symptoms-causes/syc-20361635

  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. […] Most babies with XLA appear healthy for the first few months. They’re protected by the proteins called antibodies they got from their mothers before birth. […] When these antibodies leave their systems, the babies begin to get repeat bacterial infections. The infections can be life-threatening. Infections might involve the ears, lungs, sinuses and skin. […] Male infants born with XLA have very small tonsils and small or no lymph nodes. […] People with XLA can live mostly typical lives. They should try to take part in regular activities for their ages. But repeat infections linked to XLA will likely need careful watching and treatment. They can damage organs and be life-threatening.

• #3 Bruton’s agammaglobulinemia in an adult male due to a novel mutation: a case report – Xu – Journal of Thoracic Disease

  https://jtd.amegroups.org/article/view/10008/html

  X-linked agammaglobulinemia (XLA) is caused by mutation in the gene coding for Brutons tyrosine kinase (BTK), which impairs peripheral B cell maturation and hypogammaglobulinemia. The patient had a history of recurrent respiratory tract infection which eventually progressed to chronic type II respiratory failure. Patients with XLA are particularly susceptible to respiratory infections. In our patient, Lower respiratory tract secretion specimens were obtained on bronchoscopy at the time of endotracheal intubation for respiratory failure. BTK mutations lead to impaired humoral immunity, thus rendering the patient susceptible to Streptococci, Neisseria, Enterovirus and other pathogens. The patient had a B (CD19+, CD20+) lymphocyte count of nearly 0% and low levels of IgG, IgM and IgA. This case highlights the need for a high degree of suspicion for XLA on the part of clinicians to avoid missed diagnosis.

• #3 Co-Occurring X-Linked Agammaglobulinemia and X-Linked Chronic Granulomatous Disease: Two Isolated Pathogenic Variants in One Patient

  https://www.mdpi.com/2227-9059/11/3/959

  XLA, in the past, thought easily managed and complications avoided with rapid initiation of immunoglobulin replacement, now has a known association with autoimmunity/inflammatory conditions, including diarrhea and IBD-like enteropathy. […] This case brings up thought-provoking questions about a possible mechanism for co-occurring XLA and X-CGD, which requires further study, and the development of new treatment strategies for patients with inborn errors of immunity (IEI).

• #3 X-linked agammaglobulinemia – Wikipedia

  https://en.wikipedia.org/wiki/X-linked_agammaglobulinemia

  X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body’s ability to fight infection. Patients with untreated XLA are prone to develop serious and even fatal infections. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. Children are generally asymptomatic until 69 months of age when maternal IgG decreases. Present with recurrent infections with Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, hepatitis virus, and enterovirus CNS infections. Examination shows lymphoid hypoplasia (tonsils and adenoids, no splenomegaly or lymphadenopathy). There is significant decrease in all immunoglobulins. 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, as well as low levels of all antibody classes, including IgG, IgA, IgM, IgE and IgD. With treatment, the number and severity of infections is reduced.

• #3 Frontiers | Clinical features and mutational analysis of X-linked agammaglobulinemia patients in Malaysia

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1252765/full

  X-linked agammaglobulinemia (XLA) is a congenital immunodeficiency characterized by an early arrest in B cell differentiation, resulting in a marked reduction of peripheral B cells with a profound deficiency in all immunoglobulin isotypes. Patients with XLA have increased susceptibility to bacterial infections, predominately affecting respiratory, skin and gastrointestinal system. Pneumonia was the most common manifestation among the XLA patients (n=13), followed by otitis media (n=12), upper respiratory tract infection (n=5), cellulitis (n=4) and gastroenteritis (n=4). The median age of onset of symptoms was 12 months (range 0.3-154 months). The median age of diagnosis was 48 months (range 6-188 months). All patients except P10 had markedly reduced (0-1%) CD19+ B cells. Most of these patients (91%) exhibited very low serum IgG level. In addition, 95% and 64% patients had low IgA and IgM level as compared to the same age group, respectively. […] A complete BTK protein deficiency was observed in two patients (P6 and P7) with missense mutations affecting the kinase domain of BTK protein. In this cohort, thirteen patients had absent or minimal intracellular BTK expression (0-15%) in the monocytes.

• #3 Orphanet: X-linked agammaglobulinemia

  https://www.orpha.net/en/disease/detail/47

  Infections tend to persist throughout adulthood. Affected patients are reported to have a higher susceptibility to severe and chronic enteroviral infections. […] Some patients have a less severe clinical presentation and are not recognized as immunodeficient until 10 years of age or later. Complications of X-linked agammaglobulinemia (XLA) include progressive lung disease, chronic sinusitis, inflammatory bowel disease, arthritis, as well as neurological changes. […] Most patients with XLA lead a normal life. Life expectancy may be reduced in some patients as a result of complications such as severe infections and chronic pulmonary damage. Early therapeutic measures and treatment compliance are major prognostic factors.

• #4 X-linked agammaglobulinemia // Middlesex Health

  https://middlesexhealth.org/learning-center/diseases-and-conditions/x-linked-agammaglobulinemia

  Most babies with XLA appear healthy for the first few months. When these antibodies leave their systems, the babies begin to get repeat bacterial infections. The infections can be life-threatening. Infections might involve the ears, lungs, sinuses and skin. Male infants born with XLA have: Very small tonsils. Small or no lymph nodes. […] People with XLA can live mostly typical lives. They should try to take part in regular activities for their ages. But repeat infections linked to XLA will likely need careful watching and treatment. They can damage organs and be life-threatening.

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