Running head: Case study of X-linked Agammaglobulinemia.

XLA Case Study

1. What are the cellular/molecular mechanisms that underlie this disease? (What are actual

“abnormalities” or “deficiencies” causing the disease?)

The cellular and molecular mechanisms that underlie X-linked Agammaglobulinemia are a

deficiency in B cells and antibodies. People have few B cells because there is a mutation in

the BTK gene. The absence of functional BTK protein blocks B cell development and leads

to a lack of antibodies. There is also also an absence or reduction size of peripheral lymph

nodes (Schwartz, 2017).

2. How common is this disease? Are there any particular susceptibility groups?

(Be sure to also consider any genetic or environmental susceptibilities.)

XLA is found approximately 1 in 250,000 newborns (Schwartz, 2017). Two-third of cases

of XLA are familial. Having a family member affected with XLA puts you at risk for having

a child affected with XLA. Since XLA is X-linked, males are commonly affected more than

females.

3. What are the disease symptoms?

The clinical presentation of XLA includes recurrent infections that persist during childhood

and adult years (Schwartz, 2017). The infections are usually near the surfaces of mucous

membranes such as the middle ear, lungs, and sinuses (Blaese, 2013).
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Many young boys affected develop otitis media, pneumonia, and sinopulmonary infections

(Schwartz, 2017). These infections cause patients to have fever, chills, inflammation, and

pain.

4. What mechanisms are responsible for these disease symptoms? (Note: this is different

from the answer to question 1.)

Mutations in the BTK gene lead to XLA. This gene codes for instructions on making the

BTK protein which is important in B cell development. (“NIH”, 2018). This mutation often

leads to an absence of B cells and thus the absence of antibodies. The lack of antibodies lead

to infections that don’t clear up. When infections remain, this causes the inflammatory

response to infection to remain unchecked.

5. How is the diagnosis made? What particular clinical tests are used to make this

diagnosis? This answer needs to be precise and specific. For example, “blood test” is not a

sufficient answer. Your answer must indicate what cellular or molecular components are

measured and how, and what particular parameters are used to make the disease diagnosis.

The diagnosis of XLA should be considered in patients with recurrent who have small tonsils

and absent lymph nodes (Blaese, 2013). Initial studies consist of blood levels of B cells and

the different immunoglobulins (IgG, IgM, and IgA). Blood levels of immunoglobulin should

be assessed after 6 months of age. Infants less than 6 months often have maternal antibodies

which can affect blood test results (Schwartz, 2017). If the immunoglobulins and B cells are
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absent or low, then that points to a XLA diagnosis. To confirm this, a blood test for the BTK

protein can be done (Blaese, 2013). Absent levels or low levels of BTK point to a XLA

diagnosis.

6. What is the prognosis for someone with this disease?

Most patients affected by XLA are able to live normal lives (Blaese, 2013). The

prognosis is good if patients are diagnosed early and get treated with regular intravenous gamma

globulin therapy (Schwartz, 2017). Ideally, patients should be treated before they start getting

recurrent infections. Treatment should start at the age of 10-12 weeks (Schwartz, 2017).
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References

X-linked agammaglobulinemia - Genetics Home Reference. (2018, March 27). Retrieved

April 02, 2018, from https://ghr.nlm.nih.gov/condition/x-linked-agammaglobulinemia#genes

R. S. (2017, June 13). Bruton Agammaglobulinemia. Retrieved April 02, 2018, from

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

Blaese, M. (n.d.). IDF Patient & Family Handbook or Primary Immunodeficiency

Diseases, 5th Edition (5th ed.). (2013) Immune Deficiency Foundation.