WHAT IS SCID?
Severe Combined Immunodeficiency
Disease (SCID) is a primary immune
deficiency caused by several
different genetic defects in the
immune system. It is a rare,
potentially fatal syndrome of
diverse genetic cause in which there
is combined absence of both cell-
mediated (T-lymphocyte) and
humoral (B-lymphocyte) immunity.
Besides, in many cases also involved
natural killer or NK lymphocyte
function. These defects lead to
extreme susceptibility to serious
infections. There are currently
twelve known genetic causes of
SCID. The different genetic causes of
SCID vary with respect to laboratory
findings and patterns of
inheritance. These all occurrence
of a block in T-cell
differentiation together with a
direct or indirect impairment of
B-cell immunity.
Generally, infants with SCID will
appear healthy at first during their
birth but they are highly susceptible
to severe infections as the condition
is fatal, usually within the first year
or two of life, unless infants receive
immune restoring treatments such
as transplants of blood-forming
stem cells, gene therapy or enzyme
therapy. Currently, more than 80%
of SCID infants do not have a family
history of the condition.
Fortunately, continuous research
and development of a newborn
screening test had been invented. It
helps to detect SCID before
symptoms appear and helps to
ensure that affected infants receive
life-saving treatments.
Common Form of SCID
Deficiency of the Common Gamma
Chain of the T-Cell Receptor (X-
SCID)
Most common form of SCID
(nearly 45%)
Due to a mutation in a gene on
the X chromosome that encodes a
component (referred to γc, for
common gamma chain) or chain
shared by the T-cell growth factor
receptor and other growth factor
receptors
Mutations in this gene result in
very low T-lymphocyte and NK-
lymphocyte counts
But B-lymphocyte count is high
(so-called T-, B+, NK- phenotype)
Despite the high number of B-
lymphocytes, there is no B-
lymphocyte function as the B-
cells have abnormal receptors for
growth factors on their cell
surfaces
This deficiency is inherited as an
X-linked recessive trait
Therefore, only males have this
type of SCID while the females
may be the carrier
Enzyme Adenosine Deaminase
(ADA) Deficiency
Second most common form of
SCID (about 15%)
enzyme ADA is encoded by a gene
located on chromosome 20q13.11
ADA is essential for the metabolic
function of a variety of body cells
especially T-cells
Absence of this enzyme leads to
an accumulation of toxic
metabolic by-products within
lymphocytes that cause the cells
to die.
Babies will have the lowest total
lymphocyte counts of all, and T, B
and NK-lymphocyte counts are all
very low
This deficiency is inherited as an
autosomal recessive trait
Therefore, both boys and girls
can be affected
Lack of ADA enzyme leads to
neurological problems such as
cognitive impairment, hearing
and visual impairment, low
muscle tone and movement
disorders. The neurological
problems are not fully curable by
bone marrow transplantation.
Treatment for SCID
Allogeneic Hematopoietic Stem Cell
Transplantation (HSCT)
Allogeneic HSCT is the most common
method used for the treatment of
SCID. It is a method that transplant
HLA-matched sibling donor or
HLA-matched unrelated donor stem
cells to the patients. Human have
different sets of protein which is
known as human leukocyte-
associated (HLA) antigens on the
surface of their cells. The set of
proteins can be identified through
special blood test. Stem cells for the
transplant can be obtained from the
bone marrow, peripheral blood or
even from cord blood from related
or unrelated donors that at least
partially match the tissue type of the
patient.The success rate of allogeneic HSCT
depends in part on how well the
HLA antigens of the donor’s stem
cells match those of the recipient’s
stem cells. The higher the number of
matching HLA antigens, the greater
the chance that the patient’s body
will accept the donor’s stem cells. In
general, patients are less likely to
develop a complication known as
graft-versus-host disease (GVHD) if
the stem cells of the donor and
patient are closely matched.
One of the most common stem cell
used is the bone marrow. In general,
the procedure for obtaining bone
marrow called “harvesting’’. The
donor is given either general
anesthesia, which puts the person to
sleep during the procedure, or
regional anesthesia, which causes
loss of feeling below the waist.
Needles are inserted through the
skin over the pelvic (hip) bone or, in
rare cases, the sternum (breastbone)
and into the bone marrow to draw
the marrow out of the bone.
Harvesting the marrow takes about
an hour. The harvested bone
marrow is then processed to remove
blood and bone fragments.
These stem cells are injected into the
bloodstream of the patient. The stem
cells are then travel to the bone
marrow, where they begin to
produce new white blood cells, red
blood cells and platelets. This
process is known as “engraftment.”
Engraftment usually occurs within
about 2 to 4 weeks after
transplantation. Doctors will
monitor it by checking blood counts
on a frequent basis. Complete
recovery of immune function takes
much longer, up to several months
for autologous transplant recipients
and 1 to 2 years for patients
receiving allogeneic or syngeneic
transplants. Doctors will evaluate
the results of various blood tests to
confirm that new blood cells are
being produced.
Enzyme Replacement Therapy
The enzyme pegademase bovine is a
modified enzyme where
modification of ADA by covalently
attaching numerous strands of the
inert polymer
monomethoxypolyethylene glycol
(PEG) or modified with strands of
polyethylene glycol (PEG) to
optimize its therapeutic effect. It is
used for enzyme replacement
therapy for the treatment of severe
combined immunodeficiency
disease (SCID) associated with a
deficiency of adenosine deaminase
(ADA).
Immunoglobulin therapy
Basically, a child that suffers SCID is
unable to create enough natural
antibodies (blood proteins that kill
germs) to fight infection. Therefore,
it is crucial to replace these missing
antibody into the child’s body to
reduce the risk of getting illness. A
treatment known as
immunoglobulin therapy will helps
to provide these missing antibodies
by purified human antibodies that
have been removed from donated
blood and is given.
Plasma is the liquid part of blood
that remains when all red blood
cells have been removed. When
donors given their blood, the red
blood cells and plasma are
separated. Then, the plasma is
pooled together and processed in
highly specialised and regulated
facilities to produce
immunoglobulin, which contains a
wide variety of antibodies.
Immunoglobulin therapy provides
temporary protection against
common childhood infection and it
is given either intravenously (into a
vein) or subcutaneously (injection
into the skin).
