Group 3 final case - Cal State LA

Final Case Study: Case #3
Rabin Anouseyan
Alex Huynh
Kimberly Rampasan
California State University, Los Angeles
Department of Biological Sciences
Case summary: patient overview
Martin Causubon, exact age unknown
 Over 5 years old and treated by pediatrician
Biological sister with no symptoms
 Severely underweight
 High susceptibility to recurrent infections
 Abnormal leukocytes
 Cell numbers
 Cellular responses
Case summary: recurrent
Recurring infections since 3 months of age
Multiple occurrences of otitis media (inner
ear infection)
Persistent cough caused by pneumonia in
both lungs
Multiple occurrences of thrush, caused by
Candida spp.
Many rashes in diaper area
Infections persisted despite treatment with
different antibiotics (amoxicillin,
Case summary: abnormal
Slightly low white blood cell count
Extremely low absolute lymphocyte count
Complete lack of T cells
Low numbers of NK cells
Presence of B cells
– Very low IgG concentration
– IgA and IgM concentrations at lower end of normal range
Mononuclear cells unreactive to:
Phytohemagglutinin (PHA)
Concanavalin A (ConA)
Pokeweed mitogen (PWM)
Specific antigens which he had been previously exposed to
Normal adenosine deaminase and purine nucleoside
Diagnosis for Case 3: X-linked
severe combined immunodeficiency
Genetic disorder
– X-linked recessive
Mutation in IL2RG gene on X chromosome
– Common γ chain of interleukin-2 receptor
• IL-2: major cytokine involved in T cell growth and
– Failure of T cell maturation due to
underdeveloped thymus
– Low or absent B cell activity due to low T cells
Most common form of SCID
– May affect 1 in 50,000
Key elements of X-SCID
Affected male with unaffected sister
Recurrent infections since young age
– Infections begin after depletion of maternal IgG
Deficiency in T cells and low numbers of natural killer
Unresponsive B cells: no response to immunizations
Low levels of immunoglobulins, particularly IgG
Failure to gain weight and grow normally
Normal adenosine deaminase and purine nucleoside
– Rules out adenosine deaminase deficiency and purine
nucleoside phosphorylase deficiency (other forms of
Diagnostic tests for X-SCID
Lymphocyte counts
 Flow cytometry using markers for T cells (CD3),
B cells (CD19) and NK cells (CD56)
 Positive result: low numbers of T cells and NK
○ Normal B cell numbers
Lymphocyte functional tests
 Use mitogens and specific antigens to induce B
cell proliferation
 Positive result: low proliferative macrophage
and B cell response
Genetic analysis: mutation in IL2RG gene
Analysis of immunoglobulin concentrations
X-SCID therapies and treatments
Bone marrow transplant
 From an allogeneic HLA-matched donor
 Provides self-renewing supply of healthy immune
 High success rate within first three months of life
Immunoglobulin treatments
Gene therapy
Aggressive antibiotic treatments at signs of
Very clean or sterile environment to minimize
pathogen exposure
Prognosis for X-SCID
Relatively normal life after successful
bone marrow transplant and continued
gamma-globulin therapy
 High level of mortality if severe
opportunistic infection takes place
before diagnosis and/or treatment of XSCID
 Occurs with most X-SCID cases: infant
mortality is common
Communicating the diagnosis
Sorry Mr. and Mrs. Causubon, I regret to inform you that your
son, Martin has been diagnosed with X-linked severe
combined immunodeficiency. X-SCID is a severe
immunodeficency which disables your son’s ability to fight
against infections. The good news is that there some
treatments that have been shown to be effective, however,
as with all treatments, we cannot guarantee full recovery.
The most common treatment for this disease is a bone
marrow transplant. If we act quickly and start treatment
immediately, the prognosis might be optimistic. Those who
undergo successful bone marrow transplants tend to leave
normal lives. Without any treatment, prognosis is very dim. I
would recommend immediate testing to determine if you or
any of your immediate family members are matches for a
bone marrow transplant.
Theoretical immunological basis
for X-SCID
T-helper (TH) cells have a main role in
activating the adaptive immune
 TH1 cytokine secretion augments response
 Activate infected macrophages
 Induce class switch in B cells
○ CD40 ligand
○ Fas ligand
Primary research article
Ravin et al., 2008.
Journal of Pediatric Endocrinology & Metabolism
X-SCID patients are characterized by very short stature (<
5th percentile)
– γC (mutated in X-SCID) has been implicated in growth hormone
(GH) signaling
Objective: examine levels of GH in normal and X-SCID
age-matched males
Methods: collected blood from patients
– Treat with GH (low levels) for 5 days
– Measure IGF-1 levels by immunoradiometric assay at day 0, 5
and 8
Major results: significant reduction of IGF-1 in X-SCID
patients compared to normal patients at all time points
– Possible treatment: high-level doses of GH
IGF-1 plasma levels (ng/ml)
Key figure
 Normal males
 X-SCID males
Days after recombinant growth hormone treatment
Take Home Messages
X-SCID involves the absence of T cells, NK cells, and
nonfunctional B cells
Typical symptoms
– Rashes
– Diarrhea
– Recurrent opportunistic infections
Candida spp.
Diagnostics include genetic analysis, lymphocyte counts,
lymphocyte functional tests, and analysis of immunoglobulin
Therapy is based on genetic therapy, bone marrow transplants,
and immunoglobulin treatments
Prognosis is excellent after a successful bone marrow transplant
• Late diagnosis and treatment typically leads to infant mortality from a
severe infection

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