This document discusses severe combined immunodeficiency (SCID), a genetic disorder characterized by defective development of functional T and B cells. The document covers the causes of SCID including mutations that affect cytokine receptors, enzymes, and genes involved in lymphocyte development. Signs and symptoms of SCID are described as well as diagnostic tests including low T cell counts and lack of response to mitogens. Treatment options for SCID such as hematopoietic stem cell transplantation and gene therapy are also mentioned.

1. Asem shadid

3. • How your family history is used
• By tracking the health of your blood relatives,
specialists may be able to identify some risk factors
that could affect your current or future health. Risk
factors raise your chances of developing certain
conditions.
• The importance of knowing your family history
• Knowing your potential risks of ill health can help you
to make better decisions about prevention and
screening. It can encourage your family to live
healthier lives too. And in some cases, it can also
allow you to get involved in research aimed at
understanding, preventing and curing the particular
condition.

4. • a genetic disorder characterized by the disturbed
development of functional T cells and B cells caused by
numerous genetic mutations .
• SCID involves defective antibody response due to either direct
involvement with B lymphocytes or through improper B
lymphocyte activation due to non-functional T-helper cells.
• It is also known as the bubble baby disease and bubble boy
disease .
• SCID patients are usually affected by severe bacterial, viral, or
fungal infections early in life and often present with interstitial
lung disease, chronic diarrhea, and failure to thrive.
• These babies, if untreated, usually die within 1 year due to
severe, recurrent infections unless they have undergone
successful hematopoietic stem cell transplantation.

5. • X-linked - Most cases of SCID are due to mutations
in the gene encoding the common gamma chain
(γc), a protein that is shared by the receptors for
interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21.
• These interleukins and their receptors are involved in
the development and differentiation of T and B cells.
• The result is a near complete failure of the immune
system to develop and function, with low or absent T
cells and NK cells and non-functional B cells.
• The condition is inherited in an X-linked recessive
pattern.

6. • Adenosine deaminase deficiency - caused by a
defective enzyme, adenosine deaminase (ADA),
necessary for the breakdown of purines.
• Lack of ADA causes accumulation of dATP. This
metabolite will inhibit the activity of ribonucleotide
reductase .
• Without functional ribonucleotide reductase,
lymphocyte proliferation is inhibited and the immune
system is compromised.

7. • Purine nucleoside phosphorylase deficiency - An
autosomal recessive disorder involving mutations of the
purine nucleoside phosphorylase (PNP) gene.
• Impairment of this enzyme causes elevated dGTP levels
resulting in T-cell toxicity and deficiency.
• Omenn syndrome - mutations of the RAG-1 or RAG-2
genes prevent V(D)J recombination, causing SCID.
• V(D)J recombination, less commonly known as
somatic recombination, is the unique mechanism of
genetic recombination that occurs only in developing
lymphocytes during the early stages of T and B cell
maturation.

8. • Bare lymphocyte syndrome - MHC class II is
not expressed on the cell surface of all antigen
presenting cells. Autosomal recessive. The
MHC-II gene regulatory proteins are what is
altered, not the MHC-II protein itself.

9. • The typical laboratory abnormalities observed in
SCID include low to absent T cell numbers and
function, as measured by T cell enumeration by
flow cytometry and T cell proliferation to
mitogens such as phytohemagglutinin (PHA) and
concanavalin A (ConA).
• Other immunologic abnormalities are seen, but
are not critical to the initial evaluation.

10. • There is usually a low absolute lymphocyte count (<2500
cells/microL). The thymus is generally small and devoid
of lymphocytes. Occasionally, the absolute lymphocyte
count is normal. This can be due to a high number of B
cells or to engraftment of transplacentally transferred
maternal T cells.
• ●Abnormalities of lymphocyte subpopulations as
determined by flow cytometry may vary depending upon
the specific molecular defect (table 1). Autologous T cells
are <300 cells/microL. However, the autologous T cell
count may be normal or high in some cases due to the
presence of maternal T cells in the peripheral circulation
or abnormal expansion of a few clones (eg, Omenn
syndrome). (See 'Diagnosis' below.)

11. • ●T cell mitogen responses are absent or extremely low, and
this is one of the most important tests to perform early.
Absence of T cell mitogen response is a crucial element in the
diagnosis of SCID. (See 'Diagnosis' below.)
• ●Cutaneous anergy to recall antigens is universal, but this test
is not reliable under one year of age. In vitro tests of T cell
antigen response may be used after the infant has been
immunized, but the diagnosis of SCID rests largely upon the
absence of T cell mitogen response. Thus, testing for antigen
response is not usually required in the context of evaluation for
SCID.
• ●Hypogammaglobulinemia is often found, but may be
obscured due to the presence of maternal immunoglobulin G
(IgG) in the blood in early infancy. Serum levels of
immunoglobulin M (IgM), immunoglobulin A (IgA), and
immunoglobulin E (IgE) are usually very low.

12. • Unexplained lymphopenia
• ●Recurrent fevers
• ●Failure to thrive (FTT)
• ●Chronic diarrhea
• ●Recurrence of severe episodes of thrush, mouth ulcers,
respiratory syncytial virus (RSV), herpes simplex virus (HSV),
varicella zoster virus (VZV), measles, influenza, or
parainfluenza 3
• ●Adverse reactions (infections) caused by live vaccines, such
as Bacillus Calmette-Guerin (BCG), rotavirus vaccine, or
varicella vaccine

13. • The absolute autologous T cell count is <300
cells/microL and the proliferative response to
mitogens such as phytohemagglutinin (PHA) is
less than 10 percent of the normal control.
• OR
• ●There are maternal T cells in the circulation.

14. • A B and T cell screen is a laboratory test to
determine the amount of T and B cells (lymphocytes)
in the blood.
• After the blood is drawn it goes through a two-step
process.
• First, the lymphocytes are separated from other
blood parts. Once the cells are separated, identifiers
are added to distinguish between T and B cells.
• The E-rosetting test identifies T cells and direct
immunofluorescence is used to identify B cells.
• Alternative Names
• Direct immunofluorescence; E-rosetting; T and B
lymphocyte assays; B and T lymphocyte assays

15. • ●The most common, widely available curative
therapy for most forms of SCID is hematopoietic cell
transplantation (HCT).
• An exception is adenosine deaminase (ADA)
deficiency, which may be treated with enzyme
replacement therapy (eg, polyethylene glycol-
adenosine deaminase [PEG-ADA]).
• Gene therapy is another possible alternative in some
forms of SCID.

16. • Vaccines help develop immunity by imitating an
infection. This type of infection, however, does not cause
illness, but it does cause the immune system to produce
T-lymphocytes and antibodies. Sometimes, after getting a
vaccine, the imitation infection can cause minor
symptoms, such as fever. Such minor symptoms are
normal and should be expected as the body builds
immunity.
• Once the imitation infection goes away, the body is left
with a supply of “memory” T-lymphocytes, as well as B-
lymphocytes that will remember how to fight that disease
in the future. However, it typically takes a few weeks for
the body to produce T-lymphocytes and B-lymphocytes
after vaccination. Therefore, it is possible that a person
who was infected with a disease just before or just after
vaccination could develop symptoms and get a disease,
because the vaccine has not had enough time to provide

17. • Thank you