Please help me answer the following clinical case questions. Please do not attem

Question

Please help me answer the following clinical case questions. Please do not attempt to answer unless you can answer all questions. Your help is greatly appreciated. Thank you.

A 9-month-old boy presents to clinic with his third episode of otitis media in the last 2 months. His other medical history includes pneumonia at the age of 7 months, for which he was hospitalized. Blood cultures at that time grew Haemophilus influenzae. His growth and physical development have been normal. Family history reveals a male cousin who died at age 14 months from pneumonia. On physical examination, there is no lymphadenopathy, and tonsillar tissue is not visualized. He has a bulging, erythematous tympanic membrane on the left. Lungs and remainder of physical examination are normal. You suspect immune deficiency and perform extensive laboratory workup. Flow cytometry reveals few circulating B-lymphocytes.

1. What is the most likely diagnosis? DiGeorge’s syndrome, X-linked agammaglobulinemia, or severe combined immunodeficiency disease?

2. Why do you think so? What are the features of this disorder?

3. What is the genetic problem, is there any difference male/female, and which division of immunity is lacking?

Explanation / Answer

Answers:

1. The diagnosis would be X-Linked agammaglobulinemia (explanation in answer 2) also called as Bruton's agammaglobulinemia. It cannot be DiGeorge's syndrome because in DiGeorge's syndrome physical abnormalities especiall craniofacial abnormalities, congenital heart defects, tetanus, thymic hypoplasia can be seen. These are not presented in the given case. This also cannot be severe combined immunodeficiency disease because severe combined immunodeficiency disease is characterized by lack of both T cells and B cells and the subject will suffer from various bacterial, viral or fungal infections due to severe immunocompromise. In the given case there is no lymphadenopathy, there are only few B cells and not T cells. So, that severe combined immunodeficiency can also be ruled out

2. X-linked agammaglobulinemia is characterized by lesser or complete absence of B lymphocytes which will result in absence of gamma globulins (antibodies). The previous infection with Haemophilus influenza (at the age of 7 months) also supports the diagnosis. Due to the lack of antibodies the patients with X-linked agammaglobulinemia often suffer with infections of H. inflluenza, Pneumococci, streptococci etc.

They often suffer with systemic infections of mucous membranes, skin , joints etc. In this case, there is bulging, eryhtematous tympanic membrane. Tonsils are also not seen (lymphoid tissues will be small or absent in X linked agammaglobulinemia) and the growth and development of subject is normal. All these signs and symptoms match with the characteristics of X-linked agammaglobulinemia

3. X-linked agammaglobulinemia is a X-linked recessive genetic disorder. Thus, males are more affected by this rare genetic disorder rather than female. Family history where male cousin succumbed to death at the age of 14 months also testifies the heriditary tendency of the disease. As there are no B cells (and due to which no gamma globulins-antibodies) this is a deficiency of Humoral immunity. Thus X linked agammaglobulinemia is also called as Humoral immuno deficiency syndrome.

Since male child has one copy of X chromosome, they are most affected while females having two copies, even one normal copy of X chromosome make them carriers rather than being affected.

In this syndrome, there is mutation of X chromosomal gene which is responsible for producing an enzyme called as Bruton's tyrosine kinase (abbreviated as Btk) (Named after its discoverer Ogden Bruton) . Btk is responsible for maturation of B-lymphocytes. Lack of Btk leads to immature pro B lymphocytes that leads humoral immunodeficiency.

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