Question

A 6-month-old infant presents with frequent infections and failure to thrive. Tests show adenosine deaminase (ADA) deficiency. Which immunodeficiency disorder is most likely responsible?

• A. Severe Combined Immunodeficiency (SCID)
• B. Hypogammaglobulinemia
• C. DiGeorge syndrome
• D. Wiskott-Aldrich syndrome

Hint:

ADA deficiency in an infant with recurrent infections = SCID.

Answer 1

The Correct Option is A

Step 1: Understanding the Question:
Adenosine Deaminase (ADA) deficiency is a classic biochemical cause of a devastating immune system failure in infants, leading to severe infections and growth issues.
Step 2: Detailed Explanation:

Pathophysiology of ADA Deficiency: Adenosine Deaminase is an enzyme involved in the purine salvage pathway. It converts adenosine and deoxyadenosine into inosine and deoxyinosine.

Toxic Accumulation: In the absence of ADA, deoxyadenosine and its derivative (dATP) accumulate to toxic levels. This is particularly harmful to lymphocytes (T-cells and B-cells), which are highly sensitive to these metabolites. High dATP inhibits ribonucleotide reductase, stalling DNA synthesis and inducing apoptosis in lymphoid precursors.

Clinical Manifestation: The result is Severe Combined Immunodeficiency (SCID). This autosomal recessive form of SCID accounts for approximately 15% of all cases. Infants present early (within the first 6 months) with recurrent viral, bacterial, fungal, and opportunistic (e.g., Pneumocystis) infections, along with persistent diarrhea and failure to thrive.

Immunology Profile: Laboratory tests typically reveal profound lymphopenia (low T, B, and NK cells) and agammaglobulinemia (low antibodies).

Differential Diagnosis: DiGeorge syndrome involves a deletion on 22q11 and thymic hypoplasia. Wiskott-Aldrich presents with the triad of eczema, thrombocytopenia, and infections. Hypogammaglobulinemia refers specifically to antibody deficiency rather than a combined T and B cell defect.

Step 3: Final Answer:
Adenosine deaminase (ADA) deficiency is the most common autosomal recessive cause of Severe Combined Immunodeficiency (SCID).