Adenosine deaminase deficiency
Encyclopedia
Adenosine deaminase deficiency, also called ADA deficiency or ADA-SCID, is an autosomal
recessive metabolic disorder that causes immunodeficiency
. It occurs in fewer than one in 100,000 live births worldwide.
It accounts for about 15% of all cases of severe combined immunodeficiency
(SCID).
ADA deficiency may be present in infancy
, childhood, adolescense, or adulthood. Age of onset and severity is related to some 29 known genotype
s associated with the disorder.
adenosine deaminase
. This deficiency results in an accumulation of deoxyadenosine
, which, in turn, leads to:
Because T cells undergo proliferation and development in the thymus, affected individuals typically have a small, underdeveloped thymus. As a result, the immune system
is severely compromised or completely lacking.
The enzyme adenosine deaminase is encoded by a gene on chromosome 20
.
ADA deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome
(chromosome 20 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
On September 14, 1990,the first gene therapy to combat this disease was performed by Dr. W. French Anderson on a four year old girl, Ashanti DeSilva, at the National Institutes of Health
, Bethesda, Maryland, U.S.A.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive metabolic disorder that causes immunodeficiency
Immunodeficiency
Immunodeficiency is a state in which the immune system's ability to fight infectious disease is compromised or entirely absent. Immunodeficiency may also decrease cancer immunosurveillance. Most cases of immunodeficiency are acquired but some people are born with defects in their immune system,...
. It occurs in fewer than one in 100,000 live births worldwide.
It accounts for about 15% of all cases of severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
(SCID).
ADA deficiency may be present in infancy
Infant
A newborn or baby is the very young offspring of a human or other mammal. A newborn is an infant who is within hours, days, or up to a few weeks from birth. In medical contexts, newborn or neonate refers to an infant in the first 28 days after birth...
, childhood, adolescense, or adulthood. Age of onset and severity is related to some 29 known genotype
Genotype
The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...
s associated with the disorder.
Pathophysiology
ADA deficiency is due to a lack of the enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
adenosine deaminase
Adenosine deaminase
Adenosine deaminase is an enzyme involved in purine metabolism. It is needed for the breakdown of adenosine from food and for the turnover of nucleic acids in tissues.-Reactions:...
. This deficiency results in an accumulation of deoxyadenosine
Deoxyadenosine
Deoxyadenosine is a deoxyribonucleoside. It is a derivative of the nucleoside adenosine, differing from the latter by the replacement of a hydroxyl group by hydrogen at the 2' position of its ribose sugar moiety. Deoxyadenosine is the DNA nucleoside A, which pairs with deoxythymidine in...
, which, in turn, leads to:
- a build up of dATP in all cells, which inhibits ribonucleotide reductase and prevents DNA synthesis, so cells are unable to divide. Since developing T cells and B cells are some of the most mitotically active cells, they are highly susceptible to this condition.
- an increase in S-adenosylhomocysteine since the enzyme adenosine deaminase is important in the purine salvage pathway; both substances are toxic to immature lymphocytes, which thus fail to mature.
Because T cells undergo proliferation and development in the thymus, affected individuals typically have a small, underdeveloped thymus. As a result, the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
is severely compromised or completely lacking.
Genetics
Chromosome 20 (human)
Chromosome 20 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 20 spans around 63 million base pairs and represents between 2 and 2.5 percent of the total DNA in cells...
.
ADA deficiency is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
(chromosome 20 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry
Genetic carrier
A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...
one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Treatment
Treatments include:- bone marrow transplantBone marrow transplantHematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
- gene therapyGene therapyGene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
- ADA enzyme in PEGPolyethylene glycolPolyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
vehicle
On September 14, 1990,the first gene therapy to combat this disease was performed by Dr. W. French Anderson on a four year old girl, Ashanti DeSilva, at the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
, Bethesda, Maryland, U.S.A.