Adenosine Deaminase Deficiency

Definition

Definition of Adenosine Deaminase Deficiency
Adenosine deaminase (ADA) deficiency accounts for about half of the autosomal recessive forms of SCIDs. ADA follows PNP in purine nucleoside catabolism, but deficiency in this enzyme causes even more severe symptoms than PNP deficiency, which is a T cell deficiency. ADA degrades toxic adenosine and deoxyadenosine, which accumulate in the cells of patients. Immature lymphoid cells are particularly sensitive to these nucleotides. In addition to immunological defect, most patients with ADA deficiency also have skeletal abnormalities.

Symptoms

Symptoms of Adenosine Deaminase Deficiency
There have been many attempts to try to relieve symptoms, as well as the disease itself, in those afflicted. Since ADA is carried in the blood, early attempts were made to relieve symptoms by transfusing blood from ADA positive humans into ADA deficient individuals. However, this procedure was quickly abandoned as ineffective, as well as toxic. Since ADA has a half-life of a few minutes, transfusions would need to be given constantly to be an effective treatment. Obviously this in itself is quite impractical. In addition, intracellular iron concentrations would increase with continuous transfusions, eventually leading to a toxic reaction.

Causes

Causes of Adenosine Deaminase Deficiency
ADA deficiency causes an increase of dATP, which inhibits S-adenosylhomocysteine hydrolase, causing an increase in S-adenosylhomocysteine. Both dATP and S-adenosylhomocysteine have toxic affects on lymphocytes, causing them to be functionally defective. The defective function is caused by a depletion of all of the dNTP pools. This causes a breakdown in DNA synthesis and repair of breaks occurring in the DNA.

Diagnosis

Diagnosis of Adenosine Deaminase Deficiency
Most individuals with adenosine deaminase deficiency are diagnosed with SCID in the first 6 months of life. In about 10 percent to 15 percent of cases, onset of immune deficiency is delayed to between 6 and 24 months of age (delayed onset) or even until adulthood (late onset). Immune deficiency in these later-onset cases tends to be less severe, causing primarily recurrent upper respiratory and ear infections. Over time, affected individuals may develop chronic lung damage, allergies, and other health problems.

Treatment

Treatment of Adenosine Deaminase Deficiency
Treatments include:

1. bone marrow transplant
2. gene therapy
3. ADA enzyme in PEG vehicle

Prognosis

Prognosis of Adenosine Deaminase Deficiency
Thus there was a need for researchers to develop alternative methods of treatment that would change the genotypes of ADA deficient humans. Since T cells, responsible for the initiation of the immune response, are manufactured in the bone marrow of human beings, bone marrow transplants from normal healthy individuals into ADA deficient humans was an approach taken to possibly change the genotype of these patients. This treatment is theoretically effective, but certain considerations must be made.

Prevention

Prevention of Adenosine Deaminase Deficiency
With the advent of recombinant genetics, new approaches in the treatment of ADA deficiency have been devised. These procedures use retroviruses to introduce synthetically made DNA into target tissues in the body, thus changing the genotype of the patient. The retroviruses are made avirulent, so that only the target gene, or ADA gene, is allowed to be transcribed and translated inside of the host's cells, thus preventing an infection from occurring.