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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