Practice questions answers primary immunodeficiency disorders

Practice questions answers

Primary immunodeficiency disorders

© Jun Wang, MD, PhD

1. C. When patients present with recurrent infections, always consider immunodeficiency. Lymphocytopenia is suggestive of lymphocytic defects, so that phenotyping of lymphocytes, as well as immunoglobulin profiles would be critical screening test. Blood culture is helpful if sepsis is suspected. Chest CT and MRI may help finding thoracic abnormalities. Monospot is for infectious mononucleosis, or other EBV infections. Oral plaque biopsy may determine the underlying pathology. All four have limited value in investigating the immune functions of this patient.

2. E. With markedly reduced T cells and low levels of B cells, and clinical presentation of recurrent infections, failure to thrive, this is most likely severe combined immunodeficiency, a condition all immunoglobulin, especially IgM, levels are reduced. Elevated IgG and normal IgM and IgA is either reactive (polyclonal), or due to plasma cell proliferation (monoclonal), such as multiple myeloma. Elevated IgM with reduced IgA and IgG is seen in hyper-IgM syndrome. Reduced IgA with normal IgM and IgG is seen in isolated IgA deficiency.

3. D. Severe combined immunodeficiency is most commonly caused by mutation of common gamma chain of interleukin receptors. This patient has male lateral relative who die at early age, and no female relatives are involve, suggesting this is like an X-linked hereditary disorder. Deletion of 22q is associated with DiGeorge syndrome. Bruton tyrosine kinase mutation is seen in X-linked agammaglobulinemia, a condition with markedly reduced B cells, but T cells are usually intact, or even increased in number. Mutation of CD40 ligand is seen in hyper-IgM syndrome. Mutation of SH2D1A is seen in X-linked lymphoproliferative syndrome, a condition with sustained T cell proliferation and inability to eliminate EBV-infected B cells.

4. D. Common variable immunodeficiency is a diagnosis of exclusion. It usually has low immunoglobulins with normal CBC. DiGeorge syndrome has abnormal facial appearance, as well as congenital heart defect, hypocalcemia due to hypoparathyroidism. Hyper-IgM syndrome usually has normal level B cells, normal or high level of IgM, but reduced IgA and IgG. X-linked agammaglobulinemia usually has markedly reduced B cells, but normal or increased T cells.

5. E. Reduced levels of all immunoglobulins, reduced B cell and normal level T cells are most compatible with X-linked agammaglobulinemia. Common variable immunodeficiency usually has low immunoglobulins with normal CBC. Isolated IgA deficiency can only be diagnosed in a patient older than 4, with reduced IgA but normal IgG and IgM, in the ABSENCE of other causes of hypogammaglobulinemia. Severe combined immunodeficiency is characterized by reduced levels of all immunoglobulin, especially IgM, and markedly reduced number of T cells. Transient hypogammaglobulinemia of infancy usually have normal lymphocytic subpopulations.

6. B. Bruton tyrosine kinase mutation is seen in X-linked agammaglobulinemia. Mutation of common gamma chain of interleukin receptors or adenosine deaminase are seen in severe combined immunodeficiency. Mutation of CD40 ligand on T cells is seen in hyper-IgM syndrome. Mutation of LYST/CHS is seen in Chediak-Higashi syndrome.

7. D. Normal CBC, low immunoglobulin with normal response to vaccination are most compatible with transient hypogammaglobulinemia of infancy. Common variable immunodeficiency also has low immunoglobulins with normal CBC, but usually has poor response to immunization. Isolated IgA deficiency has reduced IgA but normal IgG and IgM. Severe combined immunodeficiency is characterized by reduced levels of all immunoglobulin, especially IgM, and markedly reduced number of T cells. X-linked agammaglobulinemia has reduced levels of all immunoglobulins, reduced B cell but normal level T cells.

8. E. Hypocalcemia, heart murmur, coarse face with a history of recurrent infection and low T and B cells are most suggestive of DiGeorge syndrome, a condition with underdeveloped thymus. This patient has mildly reduced T and B cells, suggestive a partial DiGeorge syndrome, with hypoplastic thymus.

9. E. Underdeveloped parathyroid is seen in DiGeorge syndrome. Isolated congenital central nervous system defect usually has other neurological presentations, but unlikely has lymphocytic abnormality. Malnutrition, GI tract infections and thyroid C cell hyperplasia usually have relevant history or, anemia, leukocytosis, and less likely influence lymphocytic proliferation.

10. B. Hypocalcemia, heart murmur, coarse face with a history of recurrent infection and low T and B cells are most suggestive of DiGeorge syndrome, a condition with underdeveloped thymus. This patient has mildly reduced T and B cells, suggestive a partial DiGeorge syndrome, with hypoplastic thymus. Common variable immunodeficiency usually has low immunoglobulins with normal CBC. Isolated IgA deficiency can only be diagnosed in a patient older than 4, with reduced IgA but normal IgG and IgM, in the ABSENCE of other causes of hypogammaglobulinemia. Severe combined immunodeficiency is characterized by reduced levels of all immunoglobulin, especially IgM, and markedly reduced number of T cells. X-linked agammaglobulinemia has reduced levels of all immunoglobulins, reduced B cell but normal level T cells. All these are less likely to have special facial appearance or hypocalcemia.

11. B. The most common cause of death for DiGeorge syndrome is congenital heart disease.

12. A. Deletion of 22q is associated with DiGeorge syndrome. Bruton tyrosine kinase mutation is seen in X-linked agammaglobulinemia. Mutation of CD40 ligand on activated T cells is seen in hyper-IgM syndrome. Mutation of LYST/CHS is seen in Chediak-Higashi syndrome. Mutation of SH2D1A is seen in X-linked lymphoproliferative syndrome, a condition with sustained T cell proliferation and inability to eliminate EBV-infected B cells.

13. B. Neutropenia, normal level B cells, normal or high level of IgM, but reduced IgA and IgG, is seen in hyper-IgM syndrome. Common variable immunodeficiency usually has low immunoglobulins including IgM, but with normal CBC. Isolated IgA deficiency has reduced IgA but normal IgG and IgM. Severe combined immunodeficiency is characterized by reduced levels of all immunoglobulin, especially IgM, and markedly reduced number of T cells. X-linked agammaglobulinemia has reduced levels of all immunoglobulins, reduced B cell but normal level T cells.

14. C. Mutation of CD40 ligand on activated T cells is seen in hyper-IgM syndrome. Bruton tyrosine kinase mutation is seen in X-linked agammaglobulinemia. Mutation of common gamma chain of interleukin receptors or adenosine deaminase are seen in severe combined immunodeficiency. Mutation of LYST/CHS is seen in Chediak-Higashi syndrome. Mutation of SH2D1A is seen in X-linked lymphoproliferative syndrome, a condition with sustained T cell proliferation and inability to eliminate EBV-infected B cells.

15. C. Isolated IgA deficiency has reduced IgA but normal IgG and IgM. Allergic/atopic changes are commonly seen. Dermatophytosis usually have scaling changes, but simple dermatophytosis is not always associated with immunodeficiency. For this case, the real condition is IgA deficiency. Common variable immunodeficiency usually has low immunoglobulins including IgM, but with normal CBC. Severe combined immunodeficiency is characterized by reduced levels of all immunoglobulin, especially IgM, and markedly reduced number of T cells. X-linked agammaglobulinemia has reduced levels of all immunoglobulins, reduced B cell but normal level T cells.

16. A. Patients with isolated IgA deficiency commonly have IgE against IgA, that will induce anaphylactic reaction if blood products are transfused. Blood borne infection is a universal threat to any recipients of blood products, even the risk is very low. Hemolytic reactions usually occur due to mismatched blood. Hyperkalemia can be caused by old blood units, due to release of intracellular potassium. Transfusion related acute lung injury is caused by donor antibodies against recipient leukocytes.

17. A. See discussion of question 15. DiGeorge syndrome has abnormal facial appearance, as well as congenital heart defect, hypocalcemia due to hypoparathyroidism. 

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