adenosine deaminase
Summary
Adenosine deaminase (ADA) is an enzyme in the purine salvage pathway that converts adenosine and deoxyadenosine to inosine and deoxyinosine, respectively. ADA deficiency is a classic cause of severe combined immunodeficiency (SCID), the most common cause of autosomal recessive SCID. ADA levels in body fluids (e.g., pleural fluid) are also used clinically as a diagnostic marker for tuberculosis.
Detail
Pathophysiology: ADA deficiency leads to accumulation of adenosine and deoxyadenosine, which are converted to their triphosphate forms (particularly dATP) by other enzymes. Elevated dATP is toxic to lymphocytes because it inhibits ribonucleotide reductase, blocking DNA synthesis and preventing lymphocyte proliferation and maturation. This results in a severe deficiency of both B and T cells (unlike X-linked SCID, which primarily affects T cells with normal/elevated B cells), making ADA deficiency a T-cell and B-cell combined immunodeficiency—one of the few causes of SCID with low lymphocyte counts across all lineages.
Clinical significance: Infants with ADA-SCID present in the first few months of life with recurrent, severe infections (bacterial, viral, fungal, opportunistic), failure to thrive, chronic diarrhea, and skeletal abnormalities (rib-cage abnormalities). Absence of a thymic shadow on chest X-ray and thymic hypoplasia are characteristic. Treatment includes hematopoietic stem cell transplantation, enzyme replacement (PEG-ADA), or gene therapy.
Diagnostic use: Adenosine deaminase levels are elevated in tuberculous pleural effusions, ascites, and CSF (tuberculous meningitis) because activated macrophages and lymphocytes involved in the granulomatous response release ADA. High ADA levels in exudative lymphocytic pleural effusions support a diagnosis of TB, especially in high-prevalence areas, and this test has good sensitivity/specificity as an adjunct diagnostic tool.
Key associations for boards: ADA deficiency → SCID (both T and B cells low) → treat with BMT/gene therapy; ADA levels elevated in TB-related effusions.
Sources
- First Aid for the USMLE Step 1
- Robbins and Cotran Pathologic Basis of Disease
- Harrison's Principles of Internal Medicine
- Kaplan USMLE Step 1 Immunology Lecture Notes
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.