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TOPIC: ADA deficiency disorder

Submitted to:
Sir Rajeev Kant

Submitted by:
Sentirenla Longchar
B.tech (Biotechnology)
7TH Semester
I.D-12BTBIOT007

What is ADA deficiency?

Adenosine Deaminase deficiency(ADA) deficiency is an inherited disorder that


damages the immune system and causes severe combined immunodeficiency
(SCID) .people with SCID lack virtually all immune protection from bacteria,
viruses and fungi. They are prone to repeated and repeated infections that can be
very serious or life-threatening. These infections are often caused by opportunistic
organisms that do not cause illness in a person with a normal immune system.
The main symptoms of ADA deficiency are pneumonia, chronic diarrhea and
widespread skin rashes. Affected children grow much more slowly than healthy
children and some have developmental delay.

Most individuals with ADA deficiency are diagnosed with SCID in the first six
months of life. Without treatment, theses babies do not usually survive past age

two. In about 10-15 percent of cases onset of immune deficiency is delayed to


between 6 and 24 months of age or even until adulthood. Immune deficiency in
these later onset cases tends to be less severe causing primarily recurrent upper
respiratory and ear infections. Over time infected individuals may develop chronic
lung damage, malnutrition and other health problems.

Genes in ADA deficiency


Adenosine deaminase deficiency is caused by mutations in ADA genes. These
genes provide instructions for producing the enzyme adenosine deaminase. These
enzymes are found throughout the bodies most active in specialized white blood
cells called lymphocytes. These cells protect the body against potentially harmful
invaders such as bacteria and viruses, by making immune proteins called
antibodies or by directly attacking infected cells. Lymphocytes are produced in
specialized lymphoid tissues including the thymus which is a gland located behind
the breast bone and lymph nodes which are found throughout the body.
Lymphocytes in the blood and in lymphoid tissues make up the immune system.
The functions of the adenosine deaminas enzyme is to eliminate a molecule called
deoxy adenosine which is generated when DNA is broken down.deaminase
converts deoxy adenosine which can be toxic to lymphocytes, to another molecule
called deoxyinosine that is not harmful . Mutation in the ADA gene reduce or
eliminate the activity of adenosine deaminase and allow the built up of deoxy
adenosine to levels that are toxic to lymphocytes
Immature lymphocytes in the thymus are particularly vulnerable to a toxic built up
of deoxyadenosine. These cells die before they can mature to help fight infections.
The number of lymphocytes in other lymphoid tissues is also greatly reduced. The
loss of infection /fighting cells results in the signs and symptoms of SCID.

Genomic location:
Start: 44,619,519 bp from pter and 44,652,233 bp from pter
Size: 32,715 bases
Orientation: minus strand

Symptoms:
Because ADA deficiency affects the immune system, people who have the disorder
are more susceptible to all kinds of infections, particularly those of the skin,
respiratory and gastrointestinal tract. They may also be shorter than normal. Sadly
most babies are born with a disorder die within a few months.

Diagnosis:
Doctors can identify ADA deficiency during mothers pregnancy by:
(1) By taking a tiny sample of tissues from the amniotic sac where the baby
develops
(2) By looking at enzyme level fetal blood samples from the umbilical cord. After
the child is born, doctors can test a sample of his or her blood if it contains ADA.

Treatment:
There are no real cures for ADA deficiency but doctors have tried to restore ADA
levels and improve immune system functions with a variety of functions:
Bone marrow transplantation from a biological match(for example a
sibling) to provide healthy immune cell
Transfusions of red blood cells (containing high levels of ADA) from a
healthy donor
Enzyme replacements therapy involving repeated injections of the ADA
enzyme
Gene therapy/ to insert synthetic DNA containing a normal ADA gene into
immune cells

Deficiency of adenosine deaminase (ADA) results in severe combined


immunodeficiency. Clinical cure has been observed in several ADA. Severe
combined immunodeficiency patients after bone marrow transplantation in which
only donor T cells where engrafted suggesting that Tcells connection is sufficient
for full immune reconstitution. Children without an HLA matched donor have been
treated with polyethylene glycol ADA as enzyme replacement therapy resulting in
variant decrease of immunology and clinical improvement. Treatment is done by
culturing expanded T cells genetically connected by insertion of a normal ADA
gene using retroviral mediated gene with the LASN vector.

In 15-20 percent of children with severe combined immunodeficiency the


underlying defect is adenosine deaminase deficiency. The goal of the studies is to
determine the precise molecular defect in a patient with ADA deficient SCID who
previously has shown to have a total absence of ADA m RNA and a structural
alteration of the ADA gene. By detailed southern analysis we now have determine
that the structured alterations is a deletion of approximately 3.3kb which included
exon 2 and the promoter region of the ADA gene.