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Case study: Peter’s infectious diseases

Peter is 2 years of age, & has already suffered from more than his share of childhood infections & prolonged episodes of diarrhea. He has been hospitalized twice for bacterial pneumonia, has had almost constant (according to his mother) viral infections, & twice has had oral thrush (Candida albicans). He is also small for his age. Further exploration of the family tree revealed evidence of a distant great-grandparent who was perpetually “sick” & two cousins, Sally & Joe, who have recurrent infectious illnesses.

Peter’s pediatrician has referred him to your infectious diseases practice. How would you proceed?

Questions to get you started:

1. Is the gender of the patient important? Why is it significant that a great-grandparent & two cousins show similar symptoms?

2. What is the significance of the prolonged episodes of diarrhea?

3. Peter has had repeated bacterial, viral, & fungal infections. What cell type(s) or factor(s) are important to protect against these infections? Can any cell lineage(s) be ruled out on the basis of the illnesses that Peter has suffered?

4. What laboratory tests would you like to order? Why?

Simple blood tests performed on many occasions have never revealed defects in the total number of B cells & T cells or neutrophils/monocytes. However, T cell subset analysis by flow cytometry indicated severe CD4+ lymphopenia & serum immunoglobulin levels, although present, were low. Antibody titers to childhood immunizations were negligible. Nitroblue tetrazolium tests indicated a normal respiratory burst after phagocytosis.

What might be going on with Peter, & how would you proceed?

Questions to get you started:

1. Describe the underlying principle of the nitroblue tetrazolium test. Describe the flow cytometry test that was used to determine CD4+ T cell numbers.

2. Based on the following results, what immunodeficiency disorders can be ruled out?

a.) low, but detectable, serum immunoglobulins

b.) normal total numbers of T/B cells

c.) normal numbers of neutrophils & monocytes

d.) normal nitroblue tetrazolium test

3. What immunodeficiency disorders would you suspect based on the following clinical history & lab results? What further lab tests would allow you to identify – or eliminate – these immunodeficiency disorders?

a.) low CD4+ T cell numbers

b.) low serum immunoglobulin & negligible antibody titers to childhood immunizations

4. Based on the medical history & lab results, what cell lineage(s) can now be ruled out? Why, or why not?

5. What is the significance of the low antibody levels & low CD4+ T cell numbers, along with the normal total numbers of T cells, B cells, neutrophils, & monocytes?

6. Both phagocyte & B cell function tests were normal. How would you test for T cell function without the confounding variable of antigen presentation? Why is it important that phagocyte/B cell function are normal?

7. The tests for T cell function were normal, as were the tests for cell surface markers (e.g. CD28) on T cells. What should your next step be? What additional tests do you need to order?

8. Based on the available data, develop a hypothesis that explains the underlying cause of Peter’s problems. Explain. Are there any lab test(s) that could be used to verify your hypothesis?

9. What treatment would you suggest for this disorder/disease? Why?

10. Describe two genetic defects that could result in this phenotype.

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