NBME

Question 1

Wiskott Aldrich syndrome

Answer 1

Mutation in the WAS gene on the X chromosome that encodes a protein essential for actin cytoskeleton rearrangement that occurs during interactions between T lymphocytes, antigen presenting cells and B lymphocytes -> impaired innate and adaptive immune system

Question 2

What are the symptoms of Wiskott Aldrich syndrome

Answer 2

Symptoms- eczema, thrombocytopenia, infections with encapsulated bacteria and opportunistic pathogens

• petechiae and bleeding from umbilicus after separations
• susceptible to infections with S. pneumo, N. meningitidis, H. flu and opportunistic infections
• increased risk for autoimmune disease and malignancy, particularly leukemia

Question 3

Adenosine deaminase deficiency

Answer 3

Autosomal recessive mutations in the ADA gene
- can lead to development of SCID
Present with recurrent viral, bacterial and fungal infections starting at birth, failure to thrive and severe lymphopenia with impaired cellular and humoral immunity

Question 4

Severe combined immunodeficiency

Answer 4

Mutations in IL2 receptor gamma chain
Present with recurrent viral, bacterial and fungal infections starting at birth, failure to thrive and severe lymphopenia with impaired cellular and humoral immunity

• Low levels of IgG, IgM, IgA
• high levels of IgE and eosinophilia
• low levels of T cells and B cells

Question 5

Ataxia Telangiectasia

Answer 5

Autosomal recessive disorder resulting from a DNA repair defect
- increased susceptibility to hematologic malignancy such as Hodkin lymphoma
- progressive ataxia, telangiectasias, abnormal eye movements, decreased immunoglobulin concentrations (recurrent sinopulmonary infections)

Question 6

Hyper IgE syndrome

Answer 6

defect in the JAK-STAT signaling pathway
- leads to impaired Th17 cell differentiation
- present with eczema and cutaneous cold abscesses

Question 7

DiGeorge Syndrome

Answer 7

• caused by 22q11 deletion that leads to failure of the third and fourth brachial pouches to develop
  -absence leads to thymic aplasia and hypocalcemia in the setting of cardiac and craniofacial defects
• patients are susceptible to viral and fungal infections

Question 8

X linked agammaglobulinemia

Answer 8

• caused by mutations in the BTK gene that encodes a tyrosine kinase essential for all stages of B lymphocyte development and proliferation
• present with recurrent infections and low or absent immunoglobulin concentrations