Materiały źródłowe

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

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

  XLA exclusively affects males. The reported incidence and prevalence of XLA vary considerably. Some sources report that XLA occurs at a rate of 1 in 190000 live births with a frequency of 1 per 100000 newborn males, and an estimated prevalence of 1 to 9 per 1000000.[10] There is no known ethnic predisposition, but the reported incidence is highest in individuals of the White race.[15][16] […] XLA is one of the most common primary immunodeficiencies occurring in the pediatric population. Males over the age of 6 months present with recurrent infections due to encapsulated organisms because they lack the ability to produce mature B-lymphocytes and subsequently circulating immunoglobulin. This disease does not present at birth because maternal IgG provides immune defense during the earliest months of life. The initial presentations of XLA occur most commonly in the pediatric primary care and inpatient hospitalist settings. The involvement of multiple disciplines is vital to improving the outcomes of patients with XLA so that diagnosis can take place as early as possible, with streamlined treatment.

• #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 almost always affects males. But females can carry the genes linked to the condition. Most people with XLA are diagnosed in infancy or early childhood, after they’ve had repeated infections. Some people aren’t diagnosed until they’re adults. […] X-linked agammaglobulinemia is caused by a change in a gene. People with the condition can’t produce proteins called antibodies that fight infection. About 40% of people with the condition have a family member who has it.

• #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 (XLA) is a condition that only affects males. The number of people affected by XLA and how often it occurs varies significantly. One estimate places the rate of XLA at 1 in 190,000 live births, with about 1 in 100,000 newborn boys being affected. The estimated prevalence is somewhere between 1 and 9 out of every 1,000,000 people. […] X-Linked Agammaglobulinemia (XLA) is a frequent immune system disorder in children that prevents the creation of antibodies, making individuals highly susceptible to bacterial infections, viruses, and chronic diarrhea. […] The prognosis for X-Linked Agammaglobulinemia (XLA) has significantly improved with advancements in medical treatment practices. If diagnosed early, individuals with XLA can have a better prognosis. With regular immunoglobulin replacement therapy to boost the immune system and 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 (Bruton) Agammaglobulinemia: Background, Pathophysiology, Etiology

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

  X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency disease caused by mutations in the gene coding for Bruton tyrosine kinase (BTK). […] The estimated frequency of X-linked agammaglobulinemia (XLA) is approximately 1 case per 250,000 population. Two thirds of cases are familial, and one third of cases are believed to arise from new mutations. […] The incidence of XLA around the world does not vary significantly. […] Most studies involve Northern European patients. However, no racial predilection for XLA has been established. […] Bruton agammaglobulinemia is an X-linked disease, with only male offspring being affected. […] Male infants become affected by X-linked agammaglobulinemia (XLA) when maternal antibodies decline usually after age 4-6 months. […] Children typically clinically manifest the disease at age 3-9 months with pneumonia, otitis media, cellulitis, meningitis, osteomyelitis, diarrhea, or sepsis. […] Rare cases of adults in their second decade have been diagnosed with a milder form XLA thought to be due to a mutation rather than an absence of the protein.

• #4 Clinical and Experimental Pediatrics

  https://www.e-cep.org/m/journal/view.php?doi=10.3345/kjp.2016.59.11.S49

  X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Brutons tyrosine kinase (BTK) gene mutations. […] XLA is a rare genetic disorder with an estimated prevalence of 1 in 200,000 live births. […] The previous nation-wide survey Korean population under 19 years old (2001-2005), has reported that XLA is a 5th common PID with an estimated prevalence of 1.06 person/million. […] To date, more than 1256 BTK mutations have been identified to be associated with XLA, and are literally spread over the entire domains. […] Mutations of the BTK gene are found in approximately 80% of patients with agammaglobulinemia. […] Early diagnosis and treatment is the best way to achieve a good clinical outcome, and also suspicion for XLA and gene-study for the differential diagnosis with the clinically overlapping disorders will be essential. […] Thus, constructing Korean PID registry system should be essential to much improve acknowledgement.

• #5

  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. […] The estimated minimal birth rate of XLA in the United States from 1988 through 1997 averaged 1 XLA patient/379,000 total births per year, or 1/190,000 male births per year based on total births in the United States. […] Birth rate data obtained from the Registry suggest that the minimum birth rate for XLA in the United States is approximately 1/379,000 live births for the 10 years between 1988 and 1997. […] The highest birth rate was in 1989 and was 1/288,000.

• #6 Clinical and Experimental Pediatrics

  https://www.e-cep.org/m/journal/view.php?number=20125553435

  X-linked agammaglobulinemia (XLA) is a hereditary humoral immunodeficiency that results from Brutons tyrosine kinase (BTK) gene mutations. […] XLA is a rare genetic disorder with an estimated prevalence of 1 in 200,000 live births. […] The previous nation-wide survey Korean population under 19 years old (2001-2005), has reported that XLA is a 5th common PID with an estimated prevalence of 1.06 person/million. […] To date, more than 1256 BTK mutations have been identified to be associated with XLA, and are literally spread over the entire domains. […] Mutations of the BTK gene are found in approximately 80% of patients with agammaglobulinemia. […] The delayed diagnosis and treatment will lead to chronic respiratory complication and serious end-organ damage. […] Early diagnosis and therapy, and genetic counseling should be essential to reduce mortality and morbidity. […] Thus physician should keep a suspicion for this disorder. […] Furthermore, constructing Korean PID registry system should be essential to much improve acknowledgement.

• #7 Orphanet: Non-syndromic agammaglobulinemia

  https://www.orpha.net/en/disease/detail/229717

  Prevalence is estimated to be about 1/250,000 to 1/500/000. Isolated agammaglobulinemia has been reported worldwide in all ethnic groups. […] Two forms of IA have been described based on the pattern of inheritance of the genetic defects underlying the disorder: X-linked agammaglobulinemia (XLA) which represents approximately 85% of the affected patients, and autosomal agammaglobulinemia which includes recessive and dominant cases but is far less frequent. […] X-linked, autosomal recessive and autosomal dominant cases are reported.

• #8

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

  With improved life expectancy, more efforts will be required to improve post-diagnosis organ dysfunction and quality of life. […] The racial/ethnic breakdown of patients included in this dataset is predominantly White (72.5%) and is not a complete representation of the current US population based on the most recent US census Bureau that shows White, 59.3%; Black/African, 13.6%; Hispanic/Latino, 18.9%; Asian, 6.1%; American Indian or Alaska Native, 1.3%; Native Hawaiian or Pacific Islander, 0.3%; and two or more races, 2.9%. […] Infections remain the critical contributor to morbidity and organ dysfunction in patients with XLA. […] However, it is clear from this and the longitudinal study of Italian patients that IgG replacement during the lifetime of these patients is not sufficient to control morbidity and mortality. […] Patients with XLA need alternative early diagnosis and novel treatment options to address the underlying disease and aid in the treatment and prevention of co-morbid conditions that complicate the health and impact the quality of life of these individuals.

• #8

  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 disease prevalence is estimated between 1:100,000 and 1:200,000, but the true prevalence is not known, as newborn screening strategies have not been implemented. […] The USIDNET registry database is a compilation of information from medical centers around the USA and Canada. […] The purpose of this study is to understand if clinical outcomes and treatment of XLA among US-based patients have significantly changed in the past 15 years. […] Current therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function.

• #9 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. […] Estimated prevalence is 1/350,000 to 1/700,000. Annual incidence is not known. The disorder has been reported in various ethnic groups worldwide. Only males are affected and females are asymptomatic carriers.

• #10 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. […] X-linked agammaglobulinemia is caused by a faulty gene on the X chromosome. […] Women who are carriers have a 1 in 2 chance of passing the faulty X chromosome to a child. […] X-linked agammaglobulinemia is a rare genetic disease. It causes a weakened immune system and difficulty fighting infections. […] Boys are affected more often than girls. […] Most children with this disease who are treated early can lead normal, active lives. […] 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. […] Keep in regular touch with your child’s healthcare provider, and tell your child’s school and other close contacts. This will help your child stay healthier.

• #11 252453: X-linked Agammaglobulinemia (XLA): BTK (Full Gene Sequencing) | Labcorp

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

  X-linked agammaglobulinemia (XLA), also know as Bruton’s agammaglobulinemia, is a male-limited X-linked recessive immune disorder characterized by almost complete absence of mature B cells and thus the inability to produce immunoglobulins of any class. […] Genetic testing can confirm a clinical diagnosis of XLA and detect mutation carriers within affected families. […] Mutations in BTK account for all XLA and about 85% of all primary defects in early B-cell development.

• #12 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. […] Approximately 60% of individuals with XLA are recognized as having immunodeficiency when they develop a severe, life-threatening infection such as pneumonia, empyema, meningitis, sepsis, cellulitis, or septic arthritis. […] The prognosis for individuals with XLA has improved markedly in the last 25 years as a result of earlier diagnosis, the development of preparations of gammaglobulin that allow normal concentrations of serum immunoglobulin G to be achieved, and more liberal use of antibiotics. […] 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.

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

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

  The mainstay of treatment is gammaglobulin substitution therapy (by weekly subcutaneous injection or intravenous infusion every two to four weeks) to prevent bacterial infections. […] Surveillance: Complete blood count with differential and quantitative serum immunoglobulins at least annually; chest and sinus imaging as needed to assess for chronic lung and/or sinus disease. […] It is appropriate to clarify the genetic status of at-risk male relatives as soon after birth as possible so that gammaglobulin substitution therapy can be initiated promptly in affected individuals and administration of live viral vaccines can be avoided. […] Prevalence of X-linked agammaglobulinemia is approximately 3-6:1,000,000 males in all racial and ethnic groups.

• #13 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

  In the present study, the clinical, immunological, and genetic features of 22 Malaysian patients with XLA were described. Approximately 60% of the patients manifested symptoms within the first year of life. The median age at onset of symptoms was 12 months. While, the median age at diagnosis was 48 months with a median delay in diagnosis of 26.7 months. The median age at diagnosis in our cohort was similar with the study from Iran, however, higher than other studies in North Africa and Argentina, and lower than the studies in Taiwan and China. In some countries, kappa-deleting recombination excision circle (KREC) screening in newborns is implemented to detect XLA at birth. The use of KREC assay in newborn screening may reduce diagnostic delay. […] To the best of our knowledge, this is the first XLA cohort describing clinical, immunological and genetic profiles from Malaysia. Twenty-two patients with B-cell deficiency and hypogammaglobulinemia were diagnosed with XLA using BTK genetic analysis. Variable clinical phenotypes including atypical phenotypes were observed in some patients. Flow cytometric analysis of monocyte BTK protein expression is a rapid and useful tool in detecting XLA patients and the carriers, but detectable BTK protein expression can be observed in some patients with substitution or splice site mutations. Therefore, BTK mutational analysis is needed in providing the definitive diagnosis of XLA.

• #14 Clinical and immunological analysis of patients with X-linked agammaglobulinemia – single center experience

  https://www.termedia.pl/Clinical-and-immunological-analysis-of-patients-with-X-linked-agammaglobulinemia-single-center-experience,10,21451,1,1.html

  Thirty-three boys meeting ESID definitive criteria for diagnosis of XLA were included in the study. The vast majority of patients presented very low levels of all three main immunoglobulin isotypes. The mean IgG level at diagnosis before immunoglobulin replacement therapy was 1.03 g/l. Diagnosis was established through molecular analysis. The clinical diagnosis based on clinical and laboratory symptoms was made approximately 2 years and 6 months after the onset of infections. Replacement immunoglobulin therapy was introduced at the mean age of 3 years and 5 months and was generally delayed in comparison to the disease onset. The family history for XLA was positive in 27% of patients, including two brothers, two cousins and relevant history of severe recurrent infections and deaths of very young boys on the maternal side. The frequency and type of infections are shown in Table 2. The lower respiratory tract infections were of the highest frequency: 78% of patients suffered from bronchitis, over half of them from pneumonia (51%).

• #15 Clinical and immunological analysis of patients with X-linked agammaglobulinemia – single center experience

  https://www.termedia.pl/Clinical-and-immunological-analysis-of-patients-with-X-linked-agammaglobulinemia-single-center-experience,10,21451,1,1.html

  There are some reports on clinical presentation and long-term observation on a large group of patients with XLA. It is the first clinical report on such a large group of children from one center in Poland. The mean onset of symptoms occurred at 15 months of age, while clinical diagnosis of XLA usually was made 30 months later. Respiratory tract infections were reported as the most common feature, with a predominance of lower respiratory tract infection (LRTI). Delayed or suboptimal replacement therapy may result in chronic problems, such as chronic pulmonary disease or bronchiectasis. The main goal of IgG replacement treatment is to reduce the frequency and severity of infections. Early diagnosis together with replacement immunoglobulin therapy allows a decrease in the number of infectious complications, antibiotics therapy and serious lung complications. Proper treatment warrants better quality of life. The overall prognosis in XLA is not bad until diagnosis and treatment are established before onset of chronic complications.

• #16 X-linked agammaglobulinemia | Beacon Health System

  https://www.beaconhealthsystem.org/library/diseases-and-conditions/x-linked-agammaglobulinemia?content_id=CON-20256723

  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. […] Most people with XLA are diagnosed in infancy or early childhood, after they’ve had repeated infections. […] About 40% of people with the condition have a family member who has it. […] Your healthcare professional likely will suggest that you have follow-up visits every 6 to 12 months to screen for complications of XLA.

• #17

  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. […] Among the 231 XLA patients enrolled in the Registry, respiratory infections (N=203, 88%) were the most commonly reported. […] Among those deceased (N=20) where cause of death was known (N=17), mortality was attributed to infection in most (N=12, 71%). […] Chronic lung disease, often a consequence of repeated lower respiratory tract infection (LRTI), was also a frequent complication associated with mortality (N=9, 53%).

• #17

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

  Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.5-3.3] vs. median 3.0 [IQR 1.0-5.0], p=0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.5-5.0] vs. median 2.7 [IQR 1.6-6.0], p=0.04). […] Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.4-2.4] vs. median 2.8 [IQR 1.0-5.4], p=0.0006). […] For every year increase in age at start of therapy, the odds of experiencing a LRTI was 1.216 (OR 1.216, 95% CI 1.048-1.411, p=0.01). […] 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.

• #18

  https://www.indianpediatrics.net/feb2021/feb-169-175.htm

  X-linked agammaglobulinemia (XLA) is a primary disorder of humoral immunity characterized by Bruton tyrosine kinase gene mutations resulting in a primary antibody deficiency. […] Although the incidence of enteroviral meningoencephalitis in XLA is only 1-5%, yet the mortality is quite high. […] Enteroviral infections are known to cause difficult, persistent CNS disease in children with XLA. […] In one of the largest series of 36 patients of XLA seen over two decades, CNS infections constituted a significant proportion (25%) of all infections with enteroviral infections including echo, polio and coxsackie being the most problematic. […] The prevalence of enteroviral encephalitis in XLA is reported between 1% and 3%. […] Regular IVIg therapy with adequate trough levels protects against severe bacterial infections. However, the role of high dose peripheral and intraventricular immunoglobulin for enteroviral encephalitis is debatable.

• #19 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

  Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India. This is the first attempt at nationwide data collection on XLA. […] In the present study, pneumonia and other respiratory tract infections and otitis media were the most common clinical manifestations. […] Patients with XLA are predisposed to develop pyogenic infections caused by Streptococcus pneumoniae, H. influenzae, S. aureus and P. aeruginosa. […] Survival rates of XLA vary from country to country. These are largely determined by availability of diagnostic facilities and ease of access to treatment. […] There are several difficulties in diagnosis and management of XLA in India. Because of lack of awareness, several patients are diagnosed late and have already developed chronic lung disease by the time they start receiving their immunoglobulin replacement therapy. […] However, with financial support provided by FPID; some state governments in India and several philanthropist organizations, several patients have been able to access immunoglobulin replacement therapy now.

• #20 Azthena logo with the word Azthena

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

  While X-linked agammaglobulinemia (XLA) is the most frequent cause of congenital agammaglobulinemia, accounting for about 85% of cases, other genetic types of agammaglobulinemia have been discovered. […] The prevalence of XLA varies between 1:100,000 and 1:200,000. There is no known ethnic predilection, but the White race has the highest documented occurrence. […] 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.

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

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

  X-linked agammaglobulinemia is rare. Its more common in males. Approximately 1 in 200,000 males are born with XLA. […] 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, theyll do genetic testing to look for DNA changes. […] If youre concerned about XLA, a healthcare provider canscreen you for genetic conditionsyou could pass on to your child. If youre 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. […] 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.

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