SCID (Severe Combined Immunodeficiency Disease

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

1. 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

2. 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

1. 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.

2. 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).

3. 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).