Cailin McDonald
Dr. Sturgill
MI 494G
10/11/2024
The case of Simon Brady
Simon Brady was a 2-month-24-days-old infant who was admitted to the hospital with
repeated fever for 8 days with no evident cause. He is the third child in this family,
weighing 3100 grams at full-term delivery. He passed the physical examination at birth
and had no history of illness. His parents are healthy and deny a family history of
genetic diseases. At 2 months and 16 days of age, Simon developed repeated fever
and was diagnosed with pneumonia. Because of persistent fever for 8 days and cough
for 1 day after infection treatment, he was admitted to the hospital for further diagnosis
and treatment. All pertinent labs are shown in the table below.
Simon also presented with diarrhea, low electrolyte sodium, and cytomegalovirus
infection. Whole exome sequencing was performed and it turned out Simon had a
mutation in RAG1. He did not receive further treatment and died shortly after hospital
discharge.
Lab work was as follows:
Lymphocyte populations % (cells/μL)
Normal Range
Total T cells (CD3+ CD19-)
0.00 64-73
Total B cells (CD3- CD19+)
0.00 14-21
Helper / Inducible T cells (CD3+ CD4+)
0.00 29-36
Suppressor/cytotoxic T cells (CD3+ CD8+) 0.00 24-34
Natural killer cells (CD3- CD16+ CD56+)
99.34 11-23
Immunoglobulins
IgA (g/L)
0.07 0.05-0.41g/L
IgE (IU/mL)
<5.00 <15IU/ML
IgG (g/L)
1.72 3.2-7.2g/L
IgM (g/L)
0.04 0.23-0.91g/L
1. What does Simon Brady have?
Cailin McDonald
Dr. Sturgill
MI 494G
10/11/2024
a. Simon has T cell negative B cell negative NK positive SCID. This is a type
of SCID characterized by a lack of T cells and B cells but the presence of
high amounts of natural killer cells, as seen in Simon’s lab results.
2. What does RAG1 do in the immune system?
The RAG1 gene encodes for the RAG1 protein. The RAG1 protein is part of the RAG
complex which is a protein active in B and T cells that facilitates recombination.
3. Why did he have no detectable CD3 or CD19 cells?
CD3 and CD19 are expressed only in active T cells and B cells respectively.
4. How is this different than DiGeorge Syndrome?
DiGeorge syndrome is characterized by the lack of activity or complete absence
of the thymus. Patients with DiGeorge syndrome have normal levels of B levels but the
absence of T cells. In this form of SCID, there is no absence of immune organs, and
there is a lack of both B cells and T cells.
4. Do you think Simon would have had the same disease outcome if the mutation
was in RAG2? Why or why not?
Yes. A mutation in the RAG2 gene would still have inhibited the RAG complex, and thus
caused the same disease outcome.
Cailin McDonald
Dr. Sturgill
MI 494G
10/11/2024
Source:
https://rarediseases.org/rare-diseases/severe-combined-immunodeficiency/
https://www.ncbi.nlm.nih.gov/books/NBK549798/
The immune system fifth edition by Peter Parham