Adenosine Deaminase (ADA) Deficiency 🧬:
A rare autosomal recessive disorder and one of the classical causes of Severe Combined Immunodeficiency (SCID).
Infants lack virtually all immune protection, leaving them highly vulnerable to bacterial, viral, and fungal infections.
About ℹ️
- Inheritance: Autosomal recessive ⚠️.
- Pathology: ADA deficiency → accumulation of toxic purine metabolites → lymphocyte destruction (both B & T cells).
- Consequence: Profound immunodeficiency with early presentation in infancy.
Aetiology 🧪
- Normal role: ADA enzyme degrades adenosine & deoxyadenosine (purine metabolism).
- Defect: Toxic buildup of dATP (deoxyadenosine triphosphate) in lymphocytes → apoptosis.
- Result: Severe loss of adaptive immunity (SCID phenotype).
Clinical Features 👶
- Infections: Severe, recurrent, opportunistic infections (bacterial, viral, fungal, protozoal).
- Failure to thrive: Poor growth, malnutrition due to constant illness.
- Systemic: Fatigue, myalgia, exercise intolerance (toxic metabolite accumulation).
- Other: May show skeletal, hepatic, or neurologic abnormalities in chronic cases.
Differentials 🧩
- Other forms of SCID (e.g., X-linked SCID 🔵).
- Primary immunodeficiencies affecting lymphocyte number/function (e.g., DiGeorge syndrome, agammaglobulinaemia).
Investigations 🔬
- Genetic testing: Confirms ADA gene mutations.
- Immunology:
- Profound lymphopenia (low T, B, NK cells).
- Poor lymphocyte function on assays.
- Metabolic: Elevated adenosine and deoxyadenosine metabolites in plasma/urine.
Management ❤️🩹
- Early treatment is lifesaving: Untreated ADA-SCID is fatal within the 1st year.
- Hematopoietic Stem Cell Transplant (HSCT): Curative if donor is matched sibling 👨👩👧.
- Enzyme Replacement Therapy (ERT): Pegylated ADA injections restore partial immune function.
- Gene Therapy: Emerging option – patient’s own stem cells are modified to express ADA gene 🧬.
- Other options: Mismatched donor transplant – poor outcomes, last resort.
References 📚
💡 Exam Tip
"Bubble Boy disease" 🫧
ADA deficiency is the most severe form of SCID.
Key triad: recurrent infections, failure to thrive, absent lymphocytes on flow cytometry.
HSCT from a matched sibling is the gold-standard cure.
