Common Disorders Related to Nucleotide Metabolism

Adenosine Deaminase Deficiency and Severe Combined Immunodeficiency (SCID)

Nucleotide metabolism plays a crucial role in maintaining the balance of DNA and RNA synthesis. One of the key enzymes involved in purine metabolism is adenosine deaminase (ADA). Deficiency in this enzyme leads to a rare genetic disorder known as Adenosine Deaminase Deficiency (ADA-SCID), a major cause of Severe Combined Immunodeficiency (SCID).

Understanding Adenosine Deaminase Deficiency

ADA deficiency results in the accumulation of toxic metabolites, such as deoxyadenosine and adenosine, which interfere with lymphocyte development. This leads to a profound deficiency of T-cells, B-cells, and NK-cells, severely impairing the immune response.

Symptoms of ADA-SCID

• Frequent, severe infections
• Failure to thrive
• Chronic diarrhea
• Respiratory complications
• Developmental delays

Diagnosis and Genetic Testing

ADA-SCID can be diagnosed through newborn screening, genetic tests, and lymphocyte function assays. Early diagnosis is critical to prevent life-threatening infections.

Treatment Options

The primary treatment methods include:

• Bone Marrow Transplantation: The most effective long-term treatment.
• Enzyme Replacement Therapy: Administration of PEG-ADA to compensate for the enzyme deficiency.
• Gene Therapy: Experimental therapies aim to correct the genetic defect using viral vectors.

Conclusion

Adenosine deaminase deficiency is a life-threatening disorder that necessitates early diagnosis and prompt intervention. Advancements in gene therapy offer hope for future treatments.