Makindo Medical Notes

People with SCID due to ADA deficiency lack virtually all immune protection from bacteria, viruses, and fungi.

About

• Adenosine deaminase (ADA) deficiency: A rare, autosomal recessive genetic condition.
• ADA deficiency is one of the causes of severe combined immunodeficiency (SCID), affecting both B and T lymphocytes, leaving individuals highly vulnerable to infections.

Aetiology

• Adenosine deaminase is an enzyme needed to degrade adenosine and deoxyadenosine, byproducts of purine metabolism.
• Without ADA, toxic levels of dATP (deoxyadenosine triphosphate) accumulate in lymphocytes, leading to their destruction and severe immunodeficiency.
• This results in a disorder of purine metabolism, which impairs the function of the immune system.

Clinical Features

• Severe opportunistic infections due to lack of immune defense against bacteria, viruses, and fungi.
• Failure to thrive: Affected infants have poor growth and development due to recurrent infections.
• Other systemic features include fatigue, muscle pain (myalgia), or exercise intolerance due to a buildup of toxic metabolic byproducts.

Differentials

• Other forms of SCID (e.g., X-linked SCID)
• Primary immunodeficiencies affecting lymphocytes

Investigations

• Genetic testing: To confirm mutations in the ADA gene and diagnose ADA deficiency as the cause of SCID.
• Immunological assessment: Testing lymphocyte counts and function to assess the degree of immunodeficiency.

Management

• Early intervention is critical as untreated ADA-SCID is fatal within the first year of life.
• Hematopoietic stem cell transplantation (HSCT) from a matched sibling donor is a highly successful treatment with high survival rates and excellent immune recovery.
• Other treatments include enzyme replacement therapy (ERT) to provide ADA enzyme function and gene therapy to correct the underlying genetic defect.
• Mismatched parental donor transplants have poor outcomes and should only be considered when no other treatments are available.

References

• Adenosine Deaminase Deficiency - Genetics Home Reference