Materiały źródłowe

• #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. […] Hospitalization for bacterial pneumonia, requiring intravenous antibiotics for resolution, is usually what prompts the diagnostic work-up for primary immunodeficiency. […] The average age of diagnosis is 2.5 years, and almost all cases of XLA get diagnosed before 5 years of age. […] 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. […] A typical diagnostic 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.

• #1 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 agammaglobulinemia should be considered in any individual (male or female) with recurrent or severe bacterial infections, particularly if they have small or absent tonsils and lymph nodes. […] The first screening test should be an evaluation of serum immunoglobulins. In most individuals with agammaglobulinemia, all of the immunoglobulins (IgG, IgM, IgA, IgE) are low or absent. […] If the serum immunoglobulins are low or if the healthcare provider strongly suspects the diagnosis of agammaglobulinemia, the number of B cells in the blood should be measured. 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. […] 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. Almost every family has a different variant in BTK; members of the same family, however, usually have the same mutation. The specific gene that causes ARA can be identified by genetic testing.

• #1 Orphanet: X-linked agammaglobulinemia

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

  A diagnosis of XLA should be considered in patients with recurrent or persistent otitis media, pneumonia, sinusitis, and conjunctivitis starting before age five years or severe bacterial infections such as sepsis, meningitis, cellulitis, or empyema. […] Suspicion can be confirmed with blood tests showing low serum Ig and markedly reduced B lymphocyte counts. Molecular genetic testing can also be used to establish or confirm the diagnosis.

• #1 X-Linked (Bruton) Agammaglobulinemia Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  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). The detection of IgG, IgA, IgM, and IgE levels is related to age. Typically, IgM and IgA are undetectable. All levels are reduced in males with XLA. Age-specific reference range values are available to compare with the patient’s level. […] Once antibody levels are detected as abnormally low, confirmation is attained by using fluorocytometric analysis of B-lymphocyte and T-lymphocyte markers. CD19+ B-cell levels lower than 100 mg/dL are diagnostic of XLA. On fluorocytometric analysis, T-cell values (CD4+ and CD8+) are usually increased.

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

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

  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 after protein- or polysaccharide antigen vaccines, Low or absent BTK protein or mRNA expression levels, Detection of disease-causing mutations in the Btk gene. […] Findings which suggest a diagnosis of XLA in males whose B cell levels are below the 1 to 2% threshold include all or most of the following: A history 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 results should be repeated by independent testing for confirmation before beginning treatment or seeking referrals.

• #1 X-Linked Agammaglobulinemia – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1453/

  The diagnosis of XLA can be established in a female proband with suggestive findings and a heterozygous pathogenic (or likely pathogenic) variant in BTK identified by molecular genetic testing. […] Molecular genetic testing approaches can include a combination of gene-targeted testing (single gene testing, multigene panel) and comprehensive genomic testing (exome sequencing, genome sequencing). […] Sequence analysis of BTK is performed first to detect missense, nonsense, and splice site variants and small intragenic deletions/insertions. […] Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. […] Chromosomal microarray analysis (CMA) using oligonucleotide arrays or SNP arrays to detect genome-wide large deletions/duplications (including BTK) that cannot be detected by sequence analysis.

• #1

  https://journals.lww.com/ijaa/fulltext/2023/37020/diagnosis_of_a_case_of_x_linked_agammaglobulinemia.6.aspx

  X-linked agammaglobulinemia (XLA) is a rare hereditary primary immunodeficiency disorder caused by mutation in the Brutons tyrosine kinase (BTK) gene located in the Xq22 region of the X chromosome. […] We have reported one case who is a 48-month-old boy and suffering from recurrent pneumonia, skin abscess, otitis media, and swelling of the left knee joint. […] His serum Ig levels showed an IgM level of 0.169 g/l, IgG 2.43 g/l, and IgA 0.256 g/l. […] Immunophenotyping of lymphocyte subsets showed an absence of B-cells. […] Intracellular BTK protein expression in monocytes by flow cytometry showed a markedly reduced mean fluorescence index which confirmed the diagnosis of XLA. […] This disorder is easily diagnosed by the marked deficiency or complete absence of all types of serum Ig classes.

• #1 Immunodeficiency Search

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

  1. The diagnosis should be suspected in male patients with the above infectious history, low serum IgG, IgA, IgM, and low or absent CD19+ B-cells. Molecular testing for Btk mutations confirms the diagnosis. […] XLA should be suspected in male infants with bacterial sinopulmonary infections and absent tonsillar tissue. A family history suggesting X-linked inheritance may be present but new mutations can also occur. […] Step 3: Btk Protein expression and Genetic confirmation […] Btk protein expression can be assessed by flow cytometry and is markedly reduced in XLA. This assay is typically completed within a week and can provide a rapid diagnosis for a suspected patient. In contrast, gene sequencing typically takes 2 months and whole exome sequencing can take even longer. […] If the mutation analysis is negative despite a suspicious clinical phenotype, autosomal recessive agammaglobulinemia should be considered (Mutations in the Heavy Chain, Lambda 5, Ig alpha, Ig beta, and BLNK have been described). Testing for AR agammaglobulinemia can be achieved by sanger sequencing, whole exome sequencing or whole genome sequencing.

• #1 252453: X-linked Agammaglobulinemia (XLA): BTK (Full Gene Sequencing) | Labcorp

  https://www.labcorp.com/tests/252453/x-linked-agammaglobulinemia-xla-btk-full-gene-sequencing

  Test Number 252453 […] This test covers all coding nucleotides of gene BTK, plus at least two and typically 20 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 20 flanking nucleotides in the 5 and 3 UTR. […] Confirm a clinical diagnosis of XLA; detect carriers; allow early diagnosis in family members, guiding prophylactic measures. […] Genetic testing can confirm a clinical diagnosis of XLA and detect mutation carriers within affected families.

• #1 Frontiers | Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India

  https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.612323/full

  Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India […] Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria. […] Diagnosis is based on presence of pan-hypogammaglobulinemia and absence of mature B-lymphocytes in peripheral blood. Confirmation of diagnosis requires evidence of reduced expression of Btk protein on flow cytometry (or on Western blot) and BTK gene sequencing. […] There is paucity of literature on XLA from developing countries. This is largely because of lack of awareness and dearth of appropriate diagnostic facilities. […] Facilities for molecular confirmation of diagnosis are not available at many centers in the country.

• #1

  https://journals.lww.com/md-journal/fulltext/2006/07000/x_linked_agammaglobulinemia__report_on_a_united.1.aspx

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. […] A national registry of United States residents with XLA was established in 1999 to provide an updated view of the disorder in a large cohort of patients, including a minimum estimate of the incidence of the disorder, characterization of some of its epidemiologic features, further delineation of its clinical features, and estimates of survival. […] Patients were considered to have XLA if they had 1) a mutation in the BTK gene and/or defective expression of the BTK protein, or 2) a positive family history of a maternally related lateral male relative with XLA (for example, either a mutation of the BTK gene or defective expression of the BTK protein or markedly reduced numbers of B lymphocytes in their blood [2%] and hypogammaglobulinemia), or 3) markedly reduced numbers of B lymphocytes in their blood (2%) and hypogammaglobulinemia.

• #1 X-Linked Agammaglobulinemia – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1453/

  X-linked agammaglobulinemia (XLA) is characterized by recurrent bacterial infections in affected males in the first two years of life. […] The diagnosis of XLA is established in a male proband with characteristic clinical and laboratory findings and a hemizygous BTK pathogenic variant identified by molecular genetic testing. […] The diagnosis of XLA can be established in a female proband with characteristic clinical and laboratory findings and a heterozygous pathogenic variant in BTK identified by molecular genetic testing. […] X-linked agammaglobulinemia (XLA) should be suspected in probands with the following clinical, laboratory, and family history findings. […] The diagnosis of XLA is established in a male proband with suggestive findings and a hemizygous pathogenic (or likely pathogenic) variant in BTK identified by molecular genetic testing.

• #1 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/

  XLA may resemble a number of other disorders characterized by severe hypogammaglobulinemia. The most common of these is common variable immunodeficiency (CVID), a cause of hypogammaglobulinemia in which the etiology is unknown. […] Finally, the presence of a positive family history compatible with X-linked recessive inheritance and/or molecular genetic confirmation of the mutation makes differential diagnosis possible.

• #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

  In this instance, it may be easily confused for another disorder-common variable immune deficiency (CVID). […] In the two cases of XLA diagnosed as an adult and described by us in this report, mutational analysis demonstrated hemizygous Btk mutations. This led us to subsequently reclassify the patients as having an adult-presentation of XLA rather than CVID. […] A suspicion of X-linked agammaglobulinemia given his unusual absence of CD19+ B cells prompted further evaluation for Btk 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.

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

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

  Your childs doctor will conduct a physical examination. If your child has XLA, the doctor may notice very small tonsils and lymph nodes. […] 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. […] If your childs doctor suspects XLA, he or she will order a blood test to measure the number of B-cells. A low or absent percentage of B-cells can help establish the diagnosis. […] Confirmatory testing will include genetic testing for BTK. […] Sometimes, radiology studies of the neck, chest, and abdomen or lung function studies may be necessary. […] If a newborn baby has a brother, sister, maternal cousin or maternal uncle with agammaglobulinemia, the baby is at risk and should immediately be evaluated by an immunologist who will determine what tests will need to be done. […] These usually include antibody levels in the blood, determination of circulating numbers of B-cells in the blood, and, if a known genetic diagnosis is available, confirmatory testing for both affected and carrier status can be performed.

• #1 X-linked Agammaglobulinemia – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/x-linked-agammaglobulinemia

  X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections with encapsulated bacteria. Diagnosis is by measuring immunoglobulin levels and lymphocyte flow cytometry. […] Diagnosis of X-linked agammaglobulinemia is by detecting low (at least 2 standard deviations below the mean) levels of immunoglobulins (IgG, IgA, IgM) and absent B cells (1% of all lymphocytes are CD19+ cells, detected by flow cytometry). Transient neutropenia may also be present. […] Genetic testing can be used to confirm a diagnosis but is not required. Genetic testing is usually recommended for first-degree relatives. If the mutation has been identified in family members, mutational analysis of chorionic villus, amniocentesis, or percutaneous umbilical cord blood samples can provide prenatal diagnosis.

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

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

  A diagnosis of X-linked agammaglobulinemia is usually made based on a complete medical history and physical examination of your child. In addition, multiple blood tests may be ordered to help confirm the diagnosis. […] Carrier testing for females in the family is available through molecular genetic testing of the BTK gene in addition to prenatal diagnosis (amniocentesis or chorionic villus sampling) for pregnancies where the mother is a known carrier.

• #1 XLA Screening – ImmunoIVD

  https://www.immunoivd.com/applications/newborn-screening-xla/

  Newborn screening for X-linked Agammaglobulinemia (XLA) can detect the lack of KRECs within a few days after birth, facilitating an earlier diagnosis for patients with XLA and earlier initiation of treatment. […] The non-invasive test from just a single blood spot sample, allows to screen for multiple conditions at once, including SCID, SMA, and XLA, ensuring that affected newborns receive early interventions that can drastically improve their quality of life. […] Because of its rarity, newborn screening plays a critical role in early detection, allowing for timely interventions that can prevent life-threatening infections in children. […] An in vitro diagnostic (IVD) kit intended for newborn screening for severe combined immunodeficiency (SCID) and agammaglobulinemia (XLA). […] An in vitro diagnostic (IVD) kit intended for newborn screening for severe combined immunodeficiency (SCID), agammaglobulinemia (XLA), and spinal muscular atrophy (SMA) in newborns.

• #1 Delayed diagnosis of X-linked agammaglobulinaemia in a boy with recurrent meningitis | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-019-1536-7

  X-linked agammaglobulinaemia (XLA) is a rare inherited primary immunodeficiency disease characterized by the B cell developmental defect, caused by mutations in the gene coding for Brutons tyrosine kinase (BTK), which may cause serious recurrent infections. The diagnosis of XLA is sometimes challenging because a few number of patients have higher levels of serum immunoglobulins than expected. […] The delayed diagnosis is mainly due to near-normal IgG level and normal IgA level at first episode of bacterial meningitis. Also immunity parameters were not detected during the sepsis at 5 years old. It has been reported that XLA patients carrying BTK mutation show normal levels of IgG accompanied with decreased IgM. […] Early diagnosis is important for improving the outcome of XLA. […] Absence of B cells even with normal level of serum immunoglobulin should alert physicians to further confirm the possibility of XLA. Mutational analysis of BTK gene is important for accurate diagnosis to atypical patients with XLA.

• #1

  https://link.springer.com/article/10.1007/s10875-022-01237-1

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. […] In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. […] Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.53.3] vs. median 3.0 [IQR 1.05.0], p=0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.55.0] vs. median 2.7 [IQR 1.66.0], p=0.04). […] Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.42.4] vs. median 2.8 [IQR 1.05.4], p=0.0006). […] Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

• #1 X-linked agammaglobulinemia: diagnosis at adulthood

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=101979

  X-linked agammaglobulinemia (XLA) is a primary humoral recessive immunodeficiency linked to the X chromosome, caused by a mutation of a transduction molecule called Bruton tyrosine kinase. […] Symptoms started at the age of 5 years, with upper respiratory tract infections attending multiple consults till the age of 21 without diagnosis. […] During hospitalization the diagnosis of XLA was established. […] Most of the deaths due to XLA can be prevented with an early diagnosis and prior to the development of irreversible lung damage life expectancy is similar in this group as for general population.

• #1 X-linked agammaglobulinemia – Diagnosis and treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/x-linked-agammaglobulinemia/diagnosis-treatment/drc-20361639

  Diagnosis involves a medical history of repeat infections and a physical exam. Blood tests and maybe genetic testing can confirm the diagnosis. […] Your healthcare professional likely will suggest that you have follow-up visits every 6 to 12 months to screen for complications of XLA.

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

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

  A healthcare provider can perform blood tests to determine whether you or your child have XLA. If test results show a low level of B-cells or antibodies, they’ll do genetic testing to look for DNA changes. […] There’s no cure for XLA. But treatments can help you or your child avoid serious illness. They include: Replacement immunoglobulins (RIgG). Your healthcare provider gives you donor antibodies in a vein. You’ll need this treatment at least once per month. […] If you’re concerned about XLA, a healthcare provider can screen you for genetic conditions you could pass on to your child. If you’re a carrier of the mutation that causes XLA, you have a 50% chance of passing the mutation to a child. Any male children would have XLA. If you have XLA, your female children would be carriers. A genetic counselor or the provider who ordered the testing can advise you on your options if you’re a carrier or have XLA.

• #1 Cause Diagnosis and Treatment of X-linked Agammaglobulinemia | Open Access Journals

  https://www.rroij.com/open-access/cause-diagnosis-and-treatment-of-xlinked-agammaglobulinemia.php?aid=93376

  X-Linked Agammaglobulinemia (XLA), the considerably rarer X-linked agammaglobulinemia with growth hormone deficiency (approximately 10 instances recorded), and autosomal recessive agammaglobulinemia are the three kinds of Agammaglobulinemia (ARAG). […] A mutation in the Bruton Tyrosine Kinase (BTK) gene, which is situated on the long arm of the X-chromosome, causes X-linked agammaglobulinemia. […] There is no treatment for XLA. The purpose of treatment is to strengthen the immune system, prevent infections, and aggressively treat those that do develop. […] Among the medications used to treat XLA are: Gammaglobulin. This is a type of protein found in blood that contains anti-infection antibodies. […] Persons with XLA are given antibiotics on a regular basis to prevent infections. […] Because agammaglobulinemia patients are unable to manufacture specific antibodies, the primary medical treatment is immunoglobulin replacement. (Ig). […] In patients with XLA, however, dendritic and T-cell responses to influenza are normal after administration of inactivated trivalent influenza vaccination. […] Most people with XLA who get immunoglobulin on a regular basis can live very normal lives.

• #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

  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. […] The healthcare provider will ask about your childs symptoms and health history. He or she may also ask about your familys health history. The provider will give your child a physical exam. Your child may need many blood tests to help confirm the diagnosis. […] Treatment may include replacing antibodies, treating and preventing infections, and not getting live virus vaccines.

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

  https://emedicine.medscape.com/article/884942-workup

  X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, is an inherited immunodeficiency disease caused by mutations in the gene coding for Bruton tyrosine kinase (BTK). […] The diagnosis is confirmed by abnormally low or absent numbers of mature B lymphocytes, as well as low or absent expression of the heavy chain on the surface of the lymphocyte. Conversely, T-lymphocyte levels are elevated. The definitive determinant of XLA is the complete absence of BTK ribonucleic acid (RNA) or protein. Specific molecular analysis is made by single-strand confirmation polymorphism (SSCP), direct DNA analysis, denaturing gradient gel electrophoresis, or reverse transcriptase-polymerase chain reaction to search for the BTK mutation. […] IgG levels less than 100 mg/dL support the diagnosis. […] Rarely, the diagnosis is made in adults in their second decade of life. This is thought to be due to a mutation in the protein, rather than a complete absence.

• #2 X-Linked Agammaglobulinemia – GeneReviews® – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK1453/

  X-linked agammaglobulinemia (XLA) is characterized by recurrent bacterial infections in affected males in the first two years of life. […] The diagnosis of XLA is established in a male proband with characteristic clinical and laboratory findings and a hemizygous BTK pathogenic variant identified by molecular genetic testing. […] The diagnosis of XLA can be established in a female proband with characteristic clinical and laboratory findings and a heterozygous pathogenic variant in BTK identified by molecular genetic testing. […] X-linked agammaglobulinemia (XLA) should be suspected in probands with the following clinical, laboratory, and family history findings. […] The diagnosis of XLA is established in a male proband with suggestive findings and a hemizygous pathogenic (or likely pathogenic) variant in BTK identified by molecular genetic testing.

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

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

  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 after protein- or polysaccharide antigen vaccines, Low or absent BTK protein or mRNA expression levels, Detection of disease-causing mutations in the Btk gene. […] Findings which suggest a diagnosis of XLA in males whose B cell levels are below the 1 to 2% threshold include all or most of the following: A history 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 results should be repeated by independent testing for confirmation before beginning treatment or seeking referrals.

• #2 X-linked Agammaglobulinemia: diagnosis story

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

  We first saw Saravanan in our immunology clinic in 2021. Saravanan is a 40-year-old Indian man who was referred to us to establish a proper diagnosis for his underlying illness. […] 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 X-linked Agammaglobulinemia – Immunology; Allergic Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/x-linked-agammaglobulinemia

  X-linked agammaglobulinemia is characterized by low levels or absence of immunoglobulins and absence of B cells, leading to recurrent infections with encapsulated bacteria. Diagnosis is by measuring immunoglobulin levels and lymphocyte flow cytometry. […] Diagnosis of X-linked agammaglobulinemia is by detecting low (at least 2 standard deviations below the mean) levels of immunoglobulins (IgG, IgA, IgM) and absent B cells (1% of all lymphocytes are CD19+ cells, detected by flow cytometry). Transient neutropenia may also be present. […] Genetic testing can be used to confirm a diagnosis but is not required. Genetic testing is usually recommended for first-degree relatives. If the mutation has been identified in family members, mutational analysis of chorionic villus, amniocentesis, or percutaneous umbilical cord blood samples can provide prenatal diagnosis.

• #2 X-Linked (Bruton) Agammaglobulinemia Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  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). The detection of IgG, IgA, IgM, and IgE levels is related to age. Typically, IgM and IgA are undetectable. All levels are reduced in males with XLA. Age-specific reference range values are available to compare with the patient’s level. […] Once antibody levels are detected as abnormally low, confirmation is attained by using fluorocytometric analysis of B-lymphocyte and T-lymphocyte markers. CD19+ B-cell levels lower than 100 mg/dL are diagnostic of XLA. On fluorocytometric analysis, T-cell values (CD4+ and CD8+) are usually increased.

• #2 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. […] Hospitalization for bacterial pneumonia, requiring intravenous antibiotics for resolution, is usually what prompts the diagnostic work-up for primary immunodeficiency. […] The average age of diagnosis is 2.5 years, and almost all cases of XLA get diagnosed before 5 years of age. […] 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. […] A typical diagnostic 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.

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

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

  It is important to diagnose XLA disorder accurately at an initial stage to overcome future complications. […] Clinically, agammaglobulinemia can be diagnosed through several screening procedures that mainly rely on: […] Complete blood count (CBC) with differential diagnosis and quantification of serum gamma globulins to check the level of immunoglobulins (IgG, IgA, IgM) in the serum. If the level of immunoglobulins is low or found to be nearly absent, then a B-lymphocyte phenotyping procedure is recommended. […] Serum-specific antibody titers against immunization. Patients with XLA usually don’t produce antibodies in response to vaccination against diphtheria or tetanus. […] Genetic testing to check the mutation in the BTK gene on X-chromosomes and running molecular analysis in the laboratory. […] Furthermore, various other molecular diagnostic procedures are performed to evaluate the agammaglobulinemia genetic disorder. However, any delay in the diagnosis of agammaglobulinemia would be detrimental to the prognosis and the patient’s life.

• #2 X-Linked (Bruton) Agammaglobulinemia Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  Molecular genetic testing may establish an early confirmed diagnosis of congenital agammaglobulinemia and facilitate carrier detection and prenatal diagnosis. […] In patients with X-linked agammaglobulinemia (XLA), lymphoid tissues lack germinal centers, and plasma cells are missing from the lamina propria of the gut and from bone marrow stores.

• #2

  https://journals.lww.com/ijaa/fulltext/2023/37020/diagnosis_of_a_case_of_x_linked_agammaglobulinemia.6.aspx

  Hence, BTK expression can be analyzed in monocytes or platelets by flow cytometry to confirm the diagnosis. […] Ig level measurement and flow cytometric evaluation of peripheral blood lymphocytes with intracellular BTK protein detection can play a vital role in the early diagnosis of XLA among the suspected PIDD patients. […] Flow cytometric evaluation is rapid, accurate, and less costly.

• #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. […] Diagnostic studies helpful in XLA reflect the underlying lack of development of B-cells. Thus, B-cells will be markedly reduced (1%) in the blood, bone marrow and lymph nodes and plasma cells will be absent in bone marrow, lymph nodes and the lamina propria of the intestine. Serum immunoglobulins (IgG, IgA, and IgM) will be markedly reduced, and antibody function severely compromised. Identification of a mutation in the responsible gene, Brutons Tyrosine Kinase (BTK) is the gold standard for the specific diagnosis and is especially important in genetic counseling of the patient, his parents, sisters, and maternal aunts and cousins.

• #2 252453: X-linked Agammaglobulinemia (XLA): BTK (Full Gene Sequencing) | Labcorp

  https://www.labcorp.com/tests/252453/x-linked-agammaglobulinemia-xla-btk-full-gene-sequencing

  Test Number 252453 […] This test covers all coding nucleotides of gene BTK, plus at least two and typically 20 flanking intronic nucleotides upstream and downstream of each coding exon, covering the conserved donor and acceptor splice sites, as well as typically 20 flanking nucleotides in the 5 and 3 UTR. […] Confirm a clinical diagnosis of XLA; detect carriers; allow early diagnosis in family members, guiding prophylactic measures. […] Genetic testing can confirm a clinical diagnosis of XLA and detect mutation carriers within affected families.

• #2

  https://journals.lww.com/md-journal/fulltext/2006/07000/x_linked_agammaglobulinemia__report_on_a_united.1.aspx

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency caused by mutations in the gene for Bruton tyrosine kinase (BTK) that result in the deficient development of B lymphocytes and hypogammaglobulinemia. […] A national registry of United States residents with XLA was established in 1999 to provide an updated view of the disorder in a large cohort of patients, including a minimum estimate of the incidence of the disorder, characterization of some of its epidemiologic features, further delineation of its clinical features, and estimates of survival. […] Patients were considered to have XLA if they had 1) a mutation in the BTK gene and/or defective expression of the BTK protein, or 2) a positive family history of a maternally related lateral male relative with XLA (for example, either a mutation of the BTK gene or defective expression of the BTK protein or markedly reduced numbers of B lymphocytes in their blood [2%] and hypogammaglobulinemia), or 3) markedly reduced numbers of B lymphocytes in their blood (2%) and hypogammaglobulinemia.

• #2

  https://journals.lww.com/md-journal/fulltext/2006/07000/x_linked_agammaglobulinemia__report_on_a_united.1.aspx

  Of the 201 patients entered in the Registry, 120 (59%) were demonstrated to have a mutation in the gene for BTK, and/or defective expression of the BTK protein, 117 (58%) had a positive family history of a lateral male relative with XLA, and 154 (76%) had markedly reduced numbers of B cells (2%) and hypogammaglobulinemia. […] Most patients had more than 1 criterion for establishing the diagnosis, and all fulfilled established criteria for „definitive” or „probable” XLA.

• #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

  In this instance, it may be easily confused for another disorder-common variable immune deficiency (CVID). […] In the two cases of XLA diagnosed as an adult and described by us in this report, mutational analysis demonstrated hemizygous Btk mutations. This led us to subsequently reclassify the patients as having an adult-presentation of XLA rather than CVID. […] A suspicion of X-linked agammaglobulinemia given his unusual absence of CD19+ B cells prompted further evaluation for Btk 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 Immunodeficiency Search

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

  1. The diagnosis should be suspected in male patients with the above infectious history, low serum IgG, IgA, IgM, and low or absent CD19+ B-cells. Molecular testing for Btk mutations confirms the diagnosis. […] XLA should be suspected in male infants with bacterial sinopulmonary infections and absent tonsillar tissue. A family history suggesting X-linked inheritance may be present but new mutations can also occur. […] Step 3: Btk Protein expression and Genetic confirmation […] Btk protein expression can be assessed by flow cytometry and is markedly reduced in XLA. This assay is typically completed within a week and can provide a rapid diagnosis for a suspected patient. In contrast, gene sequencing typically takes 2 months and whole exome sequencing can take even longer. […] If the mutation analysis is negative despite a suspicious clinical phenotype, autosomal recessive agammaglobulinemia should be considered (Mutations in the Heavy Chain, Lambda 5, Ig alpha, Ig beta, and BLNK have been described). Testing for AR agammaglobulinemia can be achieved by sanger sequencing, whole exome sequencing or whole genome sequencing.

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

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

  A diagnosis of X-linked agammaglobulinemia is usually made based on a complete medical history and physical examination of your child. In addition, multiple blood tests may be ordered to help confirm the diagnosis. […] Carrier testing for females in the family is available through molecular genetic testing of the BTK gene in addition to prenatal diagnosis (amniocentesis or chorionic villus sampling) for pregnancies where the mother is a known carrier.

• #2

  https://www.omim.org/entry/300755

  Allen et al. (1994) suggested that refinements in techniques for primary carrier testing and genetic mapping of XLA make possible an ordered approach to prenatal diagnosis and genetic counseling. […] Schuurman et al. (1988) demonstrated the usefulness of linked RFLP markers in identifying the carrier state and in the early diagnosis of XLA in a newborn son. […] Journet et al. (1992) demonstrated that the pregnant mother of a boy with XLA but no family history of immune disease was a carrier by demonstrating with a methylation-sensitive probe that the X-inactivation pattern was skewed in the woman’s B cells but random in her polymorphonuclear cells.

• #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. […] The diagnosis of XLA is often delayed, and can be missed if patient has a mild phenotype. […] 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

  https://link.springer.com/article/10.1007/s10875-022-01237-1

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. […] In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. […] Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.53.3] vs. median 3.0 [IQR 1.05.0], p=0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.55.0] vs. median 2.7 [IQR 1.66.0], p=0.04). […] Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.42.4] vs. median 2.8 [IQR 1.05.4], p=0.0006). […] Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

• #2 X-linked Agammaglobulinemia – Is it Really Rare?

  https://www.longdom.org/open-access/xlinked-agammaglobulinemia-is-it-really-rare-25014.html

  A patient to be diagnosed with XLA needs to fulfill one or more of these criteria: Btk gene mutation and/or defective expression of Btk protein. […] They had been having recurrent episodes of such infections, for which they were on antibiotics required at every episode of such infections. […] Hence, these patients were started on intravenous Immunoglobulin therapy, 400-500 mg/kg given once in a month, following which they showed an improvement in the IgG levels in the blood, and treatment of associated infections with appropriate antibiotics. […] The cause of death in a patient with XLA is usually severe infections. […] The diagnosis of XLA and its proper treatment will have better prognosis for the child to reach adulthood and, excel in future and become a productive member in the society.

• #2 X-Linked Agammaglobulinemia

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

  XLA can be detected through screening tests that measure immunoglobulin levels or the number of B cells in the blood. […] There is no cure for XLA, but the condition can be successfully treated.

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

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

  A healthcare provider can perform blood tests to determine whether you or your child have XLA. If test results show a low level of B-cells or antibodies, they’ll do genetic testing to look for DNA changes. […] There’s no cure for XLA. But treatments can help you or your child avoid serious illness. They include: Replacement immunoglobulins (RIgG). Your healthcare provider gives you donor antibodies in a vein. You’ll need this treatment at least once per month. […] If you’re concerned about XLA, a healthcare provider can screen you for genetic conditions you could pass on to your child. If you’re a carrier of the mutation that causes XLA, you have a 50% chance of passing the mutation to a child. Any male children would have XLA. If you have XLA, your female children would be carriers. A genetic counselor or the provider who ordered the testing can advise you on your options if you’re a carrier or have XLA.

• #2 Cause Diagnosis and Treatment of X-linked Agammaglobulinemia | Open Access Journals

  https://www.rroij.com/open-access/cause-diagnosis-and-treatment-of-xlinked-agammaglobulinemia.php?aid=93376

  X-Linked Agammaglobulinemia (XLA), the considerably rarer X-linked agammaglobulinemia with growth hormone deficiency (approximately 10 instances recorded), and autosomal recessive agammaglobulinemia are the three kinds of Agammaglobulinemia (ARAG). […] A mutation in the Bruton Tyrosine Kinase (BTK) gene, which is situated on the long arm of the X-chromosome, causes X-linked agammaglobulinemia. […] There is no treatment for XLA. The purpose of treatment is to strengthen the immune system, prevent infections, and aggressively treat those that do develop. […] Among the medications used to treat XLA are: Gammaglobulin. This is a type of protein found in blood that contains anti-infection antibodies. […] Persons with XLA are given antibiotics on a regular basis to prevent infections. […] Because agammaglobulinemia patients are unable to manufacture specific antibodies, the primary medical treatment is immunoglobulin replacement. (Ig). […] In patients with XLA, however, dendritic and T-cell responses to influenza are normal after administration of inactivated trivalent influenza vaccination. […] Most people with XLA who get immunoglobulin on a regular basis can live very normal lives.

• #2 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. […] The healthcare provider will ask about your childs symptoms and health history. He or she may also ask about your familys health history. The provider will give your child a physical exam. Your child may need many blood tests to help confirm the diagnosis. […] Treatment may include replacing antibodies, treating and preventing infections, and not getting live virus vaccines.

• #2 Content – Health Encyclopedia – University of Rochester Medical Center

  https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=90&contentid=p01666

  How is X-linked agammaglobulinemia diagnosed in a child? The healthcare provider will ask about your childs symptoms and health history. They may also ask about your familys health history. The provider will give your child a physical exam. Your child may need many blood tests to help confirm the diagnosis. […] Treatment may include replacing antibodies, treating and preventing infections, and not getting live virus vaccines. […] A woman can get tested for the gene. If you are a known carrier, you can also have prenatal testing to find out if your child has inherited the gene. This might be amniocentesis or chorionic villus sampling.

• #3

  https://www.omim.org/entry/300755

  A number sign (#) is used with this entry because X-linked agammaglobulinemia/hypogammaglobulinemia (XLA) is caused by mutation in the gene encoding Bruton tyrosine kinase (BTK; 300300) on chromosome Xq22. […] X-linked agammaglobulinemia is an immunodeficiency characterized by failure to produce mature B lymphocytes and associated with a failure of Ig heavy chain rearrangement. The defect in this disorder resides in BTK, also known as BPK or ATK, a key regulator in B-cell development (Rawlings and Witte, 1994). […] The X-linked form accounts for approximately 85 to 90% of cases of the disorder. […] Fearon et al. (1987) used a strategy similar to that of Conley et al. (1986) to show that the defect in XLA is intrinsic to B cells as well as to detect the carrier state. […] According to their strategy, recombinant DNA probes simultaneously detect RFLPs and patterns of methylation of X-chromosome genes.

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

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

  Your childs doctor will conduct a physical examination. If your child has XLA, the doctor may notice very small tonsils and lymph nodes. […] 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. […] If your childs doctor suspects XLA, he or she will order a blood test to measure the number of B-cells. A low or absent percentage of B-cells can help establish the diagnosis. […] Confirmatory testing will include genetic testing for BTK. […] Sometimes, radiology studies of the neck, chest, and abdomen or lung function studies may be necessary. […] If a newborn baby has a brother, sister, maternal cousin or maternal uncle with agammaglobulinemia, the baby is at risk and should immediately be evaluated by an immunologist who will determine what tests will need to be done. […] These usually include antibody levels in the blood, determination of circulating numbers of B-cells in the blood, and, if a known genetic diagnosis is available, confirmatory testing for both affected and carrier status can be performed.

• #3 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

  Common variable immune deficiency (CVID), one of the most common primary immunodeficiency diseases presents in adults, whereas X-linked agammaglobulinemia (XLA), an inherited humoral immunodeficiency, is usually diagnosed early in life after maternal Igs have waned. […] The typical finding of absent B cells should suggest XLA rather than CVID and may be a sensitive test to detect this condition, leading to the more specific test (Btk mutational analysis). Further confirmation may be by mutational analyses. […] 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. […] A diagnosis of XLA can have significant implications including family counseling, detecting female carriers, and early intervention and treatment of affected male descendents.

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

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

  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 after protein- or polysaccharide antigen vaccines, Low or absent BTK protein or mRNA expression levels, Detection of disease-causing mutations in the Btk gene. […] Findings which suggest a diagnosis of XLA in males whose B cell levels are below the 1 to 2% threshold include all or most of the following: A history 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 results should be repeated by independent testing for confirmation before beginning treatment or seeking referrals.

• #3 Orphanet: Diagnosis of X-linked agammaglobulinemia (BTK gene)

  https://www.orpha.net/en/diagnostic-tests/diagnostic/595886?country=&name=

  Diagnosis of X-linked agammaglobulinemia (BTK gene) […] Post-natal diagnosis […] Sequence analysis: entire coding region Sanger sequencing […] Detection of microdeletions/microduplications MLPA based techniques […] List of diseases tested (1) X-linked agammaglobulinemia […] List of genes tested (1) BTK.

• #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

  Clinical features and mutational analysis of X-linked agammaglobulinemia patients in Malaysia […] X-linked agammaglobulinemia (XLA) is caused by mutation in the BTK gene, which results in very low or absent B cells. […] Genetic testing confirmed that eleven mothers and seven sisters were carriers for the disease, while three mutations were de novo. […] The combination of flow cytometric assessment and BTK genetic analysis provides a definitive diagnosis for XLA patients, especially with atypical clinical presentation. […] In addition, it may also allow carrier detection and assist in genetic counselling and prenatal diagnosis. […] XLA was clinically diagnosed according to the European Society for Immunodeficiencies criteria: having less than 2% peripheral B lymphocytes, low to undetectable levels of serum immunoglobulins, and increased susceptibility to bacterial infections.

• #3 X-linked agammaglobulinemia – VALINTERMED treatment in Valencia

  https://valintermed.com/en/medlibrary/chromosomal-agammaglobulinemia/

  X-linked agammaglobulinemia is a rare inherited immunodeficiency disorder characterized by the absence or deficiency of immunoglobulins in the blood. […] Diagnosis of X-linked agammaglobulinemia involves several steps: […] Major symptoms of the disease may include recurrent bacterial infections, chronic sinusitis and pneumonia. […] Laboratory studies usually reveal significant decreases in levels of all classes of immunoglobulins, especially IgG, IgA, and IgM. […] Other types of diagnostic tests include molecular genetic tests that help identify mutations in the BTK gene. […] Differential diagnosis is important to exclude other forms of primary immunodeficiency, such as common variable immunodeficiency. […] How is agammaglobulinemia diagnosed? Diagnosis includes immunoglobulin tests, genetic testing, and assessment of symptoms.

• #3 X-linked-agammaglobulinaemia

  https://dermnetnz.org/topics/x-linked-agammaglobulinaemia

  X-linked agammaglobulinaemia can be diagnosed on investigations including: […] Initial evaluation of serum immunoglobulins […] Measurement of B-cells in peripheral blood if initial testing reveals low serum immunoglobulins […] Molecular analysis, involving techniques such as single-strand confirmation polymorphism, DNA analysis, denaturing gradient gel electrophoresis, or reverse transcriptase polymerase tests on the BTK gene […] Genetic testing of the female relatives of a suspected X-linked agammaglobulinaemia patient […] In utero testing via chorionic villus sampling or amniocentesis […] Testing at birth for a decrease in CD19 B-cells, and an elevated level of T cells via fluorocytometric analysis.

• #3

  https://link.springer.com/article/10.1007/s10875-022-01237-1

  X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. […] In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. […] Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.53.3] vs. median 3.0 [IQR 1.05.0], p=0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.55.0] vs. median 2.7 [IQR 1.66.0], p=0.04). […] Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.42.4] vs. median 2.8 [IQR 1.05.4], p=0.0006). […] Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

• #3 X-linked agammaglobulinemia: diagnosis at adulthood

  https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=101979

  X-linked agammaglobulinemia (XLA) is a primary humoral recessive immunodeficiency linked to the X chromosome, caused by a mutation of a transduction molecule called Bruton tyrosine kinase. […] Symptoms started at the age of 5 years, with upper respiratory tract infections attending multiple consults till the age of 21 without diagnosis. […] During hospitalization the diagnosis of XLA was established. […] Most of the deaths due to XLA can be prevented with an early diagnosis and prior to the development of irreversible lung damage life expectancy is similar in this group as for general population.

• #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. […] The healthcare provider will ask about your childs symptoms and health history. He or she may also ask about your familys health history. The provider will give your child a physical exam. Your child may need many blood tests to help confirm the diagnosis. […] Treatment may include replacing antibodies, treating and preventing infections, and not getting live virus vaccines.

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