ORDER 1
 
Free Custom «X-Linked Agammaglobulinemia (XLA)» Essay Sample

Free Custom «X-Linked Agammaglobulinemia (XLA)» Essay Sample

X-linked agammaglobulinemia (XLA) refers to an inherited condition that impairs the immune system and makes the body unable to produce antibodies. As a consequence, this immunodeficiency interferes with the defense mechanisms that protect the body from viral and bacterial attacks. The primary factor that causes XLA is defect in Bruton's tyrosine kinase (BTK) gene, which prevents from normal development of B cells. Thus, individuals suffering from XLA are unable to produce antibodies as this function is performed by normal B cells only (Kawakami et al., 20110). Given that XLA is a rare genetic disease, there is a need to summarize the important information concerning the condition, including immunopathogenesis, symptoms, epidemiology, and treatment.

XLA Symptoms and Prognosis

The main symptoms associated with XLA include recurrent infections due to compromised immune response caused by defects in B-lymphocytes. These types of blood cells are responsible for production of antibodies, and in case of their malfunctioning basal serum Igs concentration reduces significantly (Khan, 2012). XLA is also associated with failure of the immune system to perform antigen-induced antibody responses against bacteria and viruses, as most classes of IgG cannot be produced (Schroeder & Cavacini, 2010). Individuals suffering from XLA experience frequent bacterial infections and the signs of the disease appear by the end of the first year of life. It is the time, when class G antibodies, donated by their mothers during breastfeeding, are cleared. 

Given that the signs of serial bacterial infections appear in the end of the first year, XLA patients are normally healthy during the first months after delivery (Akin et al., 2013). The most common bacterial infections include sinusitis, pneumonia and bronchitis, conjunctivitis, and ear infections. Individuals also tend to experience infections that lead to chronic diarrhea. Almost all reported cases of XLA have been on males, because they have a single copy of X chromosome, while females have two chromosomes of this type. However, females can act as carriers and pass the disease to their sons (Akin et al., 2013). The women carriers can be detected through identification of (BTK), which indicates the presence of defective XLA allele.

The disease prognosis significantly depends on timely administration of the required treatment to prevent persistent infections. The prognosis tends to be positive, when patients are diagnosed in time and receive timely treatment through intravenous gammaglobulin therapy. Treatment should be started before the patient attains five years of age (Schwartz & Desposito, 2017). Gammaglobulin is a mixture of antibodies that help a patient fight bacterial diseases. Since the majority of XLA patients are susceptible to viral infections, prevention of these complications can always be achieved through proper treatment (Schwartz & Desposito, 2017). It should be taken into account that enteroviral infections might be deadly in adults suffering from XLA.

Limited Time offer!

Get 19% OFF

0
0
days
:
0
0
hours
:
0
0
minutes
:
0
0
seconds
 
Code:

Genetics and Mechanisms that Underlie XLA

The XLA defect is associated with inability of the immune system to prevent infections, especially those caused by encapsulated bacteria. This defect is always accompanied by low basal serum Ig concentration and lack in antigen-induced antibody reactions against pathogens. As a result, the condition is can be described as humoral immunodeficiency that does not interfere with cellular immunity (Kawakami et al., 20110). Individuals suffering from XLA have reduced concentration of circulating B cells, or even lack this cell type completely (Chen et al., 2016). The deficiency in peripheral B lymphocytes is caused by block in development of pre-B-cells. Sometimes, some IgM+ immature B cells, which do not undergo further development, are produced. The defects in development of B cell, as well as the in immature B cells, are the primary causes of Ig deficiency (Fried & Bonilla, 2009). The early B-cells fail to mature in human due to mutation in BTK gene (Chen et al., 2016). Mutations in parts of the pre-B cell receptor and intracellular structures are responsible for the rest of the sub-categories of agammaglobulinemia.

We Provide 24/7 Support

Have you got any questions?

Start Live chat

Typical Case Example

A seven years old boy is suffering from fatigue, fever, and cough. He was diagnosed with pneumonia and acute otitis. The prescribed medicine included clarythromycine and ampisillin-sulbactam. Previously, the boy had been hospitalized five times for pneumonia, suffered from had bilateral otitis media, which developed resistance to treatments for the past two years. the boy used to experience upper respiratory tract infection eight to ten times annually. The first pneumonia infection and hospitalization occurred, when he was fifteen months old. However, the boy came from a family with no history of immunodeficiency. Physical examination revealed weakness and pallor. His weight was categorized to be below the third percentile with body temperature of 36.8˚C. The boy's blood pressure and pulse rate were 100/60 mmHg and 98 per minute respectively (Akin et al., 2013). Further examination showed bilateral purulent otorrhea. The boy did not have palpable lymph nodes, while tonsillar tissue was hypoplasic. The medics performed laboratory tests and identified that concentration of white blood cells was 3850 per mL, among which the neutrophils and lymphocytes comprised 88% and 12% respectively (Akin et al., 2013). Concentration of hemoglobin was 8g per dL, while its sedimentation rate was 98mm/s, and the platelets count was 357 × 103 per mL. The doctors found C - reactive protein (CRP) to be 115 mg/L and the levels of IgG and IgM were 145 mg/L. The boy also had abnormally low levels of CD 19+ cells (B-cells).

Benefit from Our Service: Save 25%
Along with the first order offer - 15% discount, you save extra 10% since we provide 300 words/page instead of 275 words/page

The doctors prescribed and administered cefoperazone/sulbactame and teicoplanin upon admission. All the laboratory tests and history of persistent pneumonia indicated that the patient had XLA. Intravenous immunoglobulin was prescribed for two days starting from the third day of hospitalization (Akin et al., 2013). After two weeks, the patient recovered completely and was discharged. Regular treatment schedule included monthly gammaglobulin injections. This was a typical case example of XLA.

Epidemiology and Incidence Rate

The frequency, with which XLA occurs, is approximately one case per 250,000 individuals, which indicates that the condition is rare (Schwartz & Desposito, 2017). In addition, it is expected that two-thirds of incidences are associated with family history, while one third develops due to novel gene mutation. No experiment or study has ever linked XLA to a particular race. As a consequence, racial or ethnic predisposition for this condition has never been identified. XLA affects mainly males, because it is an X-linked disease (Xu et al., 2016). Most individuals, who develop this condition, have high chances for its inheritance from their parents (Chen et al., 2016). On rare occasions, XLA develops due to spontaneous mutations, which take place in immunoglobulin-alpha, lambda-5, and IGHM. Therefore, XLA is very rare disorder, which affects males mainly.

VIP Services

Get an order prepared
by Top 30 writers

10.95 USD

Get
VIP Support

9.99 USD

Get an order
Proofread by editor

4.33 USD

Get
extended REVISION

2.00 USD
3.00 USD

Get
SMS NOTIFICATIONS

5.99 USD

Get a full
PDF plagiarism report

VIP SERVICES
PACKAGE 29.01 USD20% off

VIP SERVICES
PACKAGE 29.01 USD

Male infants show the first symptoms of XLA, when antibodies donated by their mothers are cleared. It usually happens as they attain four to six months of age. If the mother is identified as an XLA carrier, fetal lymphocytes are collected during chorionic villi sampling. Birth blood samples from cord are tested to determine, if CD19+ B cells are low. A rise in mature T cells is also established (Schwartz & Desposito, 2017). Clinically, infants develop the XLA, when they are three to four months, showing signs of sepsis, pneumonia, otitis, and meningitis.

XLA Pathology

Absence of BTK functional leads to inability of maturation and differentiation of B-lymphocytes. When mature B cells are absent, the plasma cells responsible for antibody production cannot form in the body as well. Consequently, the lymphoid and reticuloendothelial tissues that provide the sites for cell proliferation remain in a poorly developed state. The sizes of the adenoids, spleen, and the lymph nodes may diminish. It was also identified that mutated BTK occurs due to activation of proto-oncogenes in different regions of the genome (Schwartz & Desposito, 2017). It was identified thorough analysis of the role of BTK’s in B-cell differentiation. An individual may develop XLA disease, when mutations occur in the five domains of the enzyme.

Top 10
writers

Get the most experienced writer
in the relevant discipline!

Hire a TOP writer for $10.95

Missense mutations are the most frequent genomic event, leading to XLA. The majority of them always result in BTK enzyme absence. Such mutations have significant effects on the cytoplasmic BTK protein levels. However, the degree of XLA disease in an individual cannot be approximated by the number and nature of mutations. Nevertheless, it is estimated that almost one third of mutations occur within CGG codons (Schwartz & Desposito, 2017). These normally encode for arginine. For B lymphocytes to differentiate and proliferate, BTK must be present and play an important role in both processes. XLA patients may have very low or zero B lymphocytes and plasma cells count. It is important to note that there is no clinical disease manifestation for female carriers.

Diagnostic Tests

The diagnosis of XLA, which is a rare disease, presents some challenges. However, health professionals use various methods for successful diagnosis. Primarily, an individual’s medical history (Nahum, Manson, & Ngan, 2015). They also consider the symptoms, conduct physical examinations, and perform laboratory tests. It is important to note that detection and diagnosis should be performed as early as possible. Under these conditions, mortality and morbidity, as well as pulmonary infections, are reduced and prevented. The confirmation of diagnosis is normally achieved by detection of unusually low levels or absence of mature B lymphocytes. It is also confirmed by abnormally low volumes or absence of µ heavy chain expression on lymphocyte surfaces.

VIP Support

VIP support services:
extra attention is guaranteed!

Hire a VIP support for $9.99

Similarly, elevation of T-lymphocytes is an indication of the problem. Lack of BTK RNA or proteins is the absolute determinant for X-linked agammaglobulinemia. The single-strand confirmation polymorphism (SSCP) is applied to perform precise molecular analysis to investigate BTK mutation and quantify variants sequence (Černi et al., 2015). Other procedures used to identify BTK mutation include direct DNA analysis (Gong et al., 2015), reverse transcriptase, and gradient or agarose gel electrophoresis (Lee et al., 2012). SSP is also useful in women tests for being carriers during prenatal evaluation (Schwartz & Desposito, 2017). This is normally performed through chronic villus sampling, particularly, when medical specialists know that the mother is a carrier. In this case, the diagnosis is confirmed, when the levels of IgG are below 100 mg per dL. XLA diagnosis is recognized in males during the specific clinical findings and detection of a variant, known as hemizygous pathogenic. It is performed by molecular genetic testing, which included comprehensive genomic, multi-gene panel, and single gene testing (Lee et al., 2012).

Still have any questions?

,

Live chat

Single Gene Testing

In this type of test, professionals conduct examination of BTK gene sequence. After the sequence investigation, duplication or deletion investigation is performed in cases, where the pathological variant is not detected. Since some small proportion of patients with the abnormal gene have significant deletions that include some components of BTK and TIMM8A gene (Arai et al., 2011), chromosomal microarray tests are recommended (Wallace & Bean, 2017). Patients with characteristics of XLA and deafness-dystonia-optic neuropathy syndrome should have chromosomal microarray tests.

Multi-Gene Panel

Multi-gene panel involves BTK and several other genes. Most females with XLA phenotype, but lack detectable BTK pathological variant most likely have the defective genes, which are essential for B-cells development (Wallace & Bean, 2017). Presence of abnormal variants of these genes is identified during panel their testing in the different manner from common laboratory diagnosis. The procedures and approaches in the panel include duplication or deletion analysis, sequence and non-sequence based testing.

Try Our Discounts

Try our service with huge discounts

Read more
up to 15% OFF

Genomic Testing

This testing includes genome and exome sequencing and is very useful, because it is performed, when both single gene and multi-gene panels do not confirm the diagnosis for a patient, who exhibits symptoms of XLA. Genome and exome sequencing remains the most affordable method to generate such information (Van et al., 2013). Comprehensive genomic testing also provides important details for diagnosis, such as mutation of different genes. Exome sequencing is a test that clinicians use to recognize and investigate the sequence of the nuclear genes involved in protein coding (Conley et al., 2012). On the other hand, genome sequencing is used to investigate the sequence of nuclear DNA in both coding and non-coding regions (Wallace & Bean, 2017). Although mitochondrial DNA is a component of the genome, its sequencing is usually requested and performed separately.

Treatment Methods

The main treatment approach is gammaglobulin substitution therapy. It is performed through intravenous infusion or subcutaneous injections. The two methods contribute to increase in IgG concentration in patients, especially children (Suri et al., 2017). However, the choice of the route used to treat an XLA patient depends on the patient's and physician's convenience. Intravenous immunoglobulin prevents inflammatory effects (Cavaliere et al., 2017). There are many types of gammaglobulin brands. However, all of them are of equal efficacy. The side effects associated with this medication include nausea, headaches, and backache. Individuals may have high chances for experiencing the adverse reactions, if they are suffering from inter-current viral infection.

Plagiarism check

  • Use our plagiarism check option to submit original papers!
Order and Check

Chronic prophylactic antibiotics may be given to avoid infections. For the infants suffering from XLA, inactivated polio vaccine (IPV) is administered, as opposed to oral polio vaccine received by healthy children. It helps to prevent them from infecting their brothers with live virus (Brickley & Wright, (2017). Their siblings are also given the IPV vaccine at about the same time. The management of XLA also involves prevention of infections and ensuring prompt treatment as they occur. The use of antibiotics helps to reduce the likelihood for developing chronic sinusitis, lung disease, and other bacterial infections. Besides, timely detection and treatment of bowel infectious disease are critical for suppression of inflammatory bowel disease.

Experimental Approach

In order to determine novel treatment options for XLA disease, a number of testing should be performed. The approach must ensure that information concerning blood count, as well differential gene expression, is obtained. It must also reveal chemical parameters, including C - reactive protein, renal, and liver tests. Other critical information that the approach must incorporate include chest and sinus x-rays, and pulmonary function.

No more grammatically incorrect texts!

  • Get your papers proofread by professionals!
Order Proofreading

Conclusion

XLA is an inherited disease that affects the immune system and makes the body unable to produce antibodies for its defense against pathogenic invasion. Symptoms of XLA include recurrent bacterial infections, low levels of basal serum Igs, and CD 19+ cells, which are indicators for maturation of B cells. The frequency of XLA is approximately one case per 250,000 individuals, implying that it is one of the rarest diseases. The main pathological change associated with XLA includes absence of BTK, which causes non-differentiation or maturation of B-lymphocytes. This makes the immune system weak, as the production of antibodies is impaired. Absence of functional enzyme is also used for confirmation of diagnosis. The main treatment option for XLA is gammaglobulin substitution therapy and use of antibiotics to prevent intercurrent and secondary diseases. Still, experimental treatment approaches are being developed.

Do you need professionally written papers?

Place your order on our website to get help from qualified experts!

Order now
Your request should consist of 5 char min.
 

Use discount code first15 and

Get 15%OFF on Your first order

Order now
x
Online - please click here to chat