Adenosine deaminase deficiency

Adenosine deaminase deficiency
ICD-10	D81.3
ICD-9	279.2
OMIM	102700
DiseasesDB	260

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Adenosine deaminase deficiency, or ADA deficiency, is an inherited immunodeficiency syndrome accounting for about 25% of all cases of severe combined immunodeficiency (SCID).

This disease is due to a lack of the enzyme adenosine deaminase coded for by a gene on chromosome 20. There is an accumulation of dATP, which causes an increase in S-adenosylhomocysteine; both substances are toxic to immature lymphoid cells, so fail to reach maturity. As a result, the immune system of the afflicted person is severely compromised or completely lacking.

The enzyme adenosine deaminase is important for purine metabolism.

Historical Perspective

Adenosine deaminase (ADA) deficiency was first discovered by Dr. Eloise Giblett in 1972, when she received samples from a patient with severe combined immunodeficiency (SCID) that was a candidate for bone marrow transplantation; examination of blood samples presented that the patients have no ADA activity. With discovering a second case with ADA deficiency and immunedeficiency, ADA deficiency was the first immunodeficiency in which the specific molecular defect was described.

Classification

There is no established system for the classification of adenosine deaminase deficiency.

Pathophysiology

Adenosine deaminase (ADA) is an ubiquitous enzyme found in all cells, It catalyzes the deamination of adenosine and deoxyadenosine to inosine and deoxyinosine. ADA deficiency is caused by mutations in the ADA1 gene at 20q13.11. In the absence of functional ADA, there is an intracellular accumulation of adenosine and deoxyadenosine which leads a buildup of dATP and prevent de novo synthesis of nucleotides and deoxynucleotides in all cells, and inhibits ribonucleotide reductase and prevents DNA synthesis.

In addition, deoxyadenosine irreversibly binds to and inhibits S-adenosylhomocysteine hydrolase, a rise 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. which also contributes to abnormal DNA synthesis.

ADA-deficient individuals typically have severely reduced numbers of T, B, and natural killer (NK) cells.

Causes

Adenosine deaminase deficiency is a disorder arising from mutation in the ADA1 gene at 20q13.11.

Treatment

Medical Therapy

• bone marrow transplant
• gene therapy (efforts halted due to increased incidence of leukemia)
• ADA enzyme in PEG vehicle
• Stem Cell Therapy(still in the experimental stage)

The first gene therapy to combat this disease was performed by Dr. W. French Anderson on a 4yr old girl, Ashanti DeSilva, in 14 September 1990 at the National Institute of Health, Bethesda, Maryland, U.S.A.

The therapy performed was the first successful case of gene therapy.

Primary Prevention

===Secondary Prevention

External links

• Gene Therapy: A Brief History: [2]