Adenosine deaminase deficiency 

Key Points 

Adenosine Deaminase Deficiency, a form of Severe Combined Immunodeficiency (SCID), is a purine metabolic disorder caused by mutations in the ADA gene, resulting in immunodeficiency and its complications. 

-It was first discovered in 1972 by American genetic scientist, Eloise Giblett.

-In 1990, it was the first pathophysiologic condition to be treated by gene therapy. 

Mechanism: The enzyme adenosine deaminase (ADA) is encoded by the ADA gene on chromosome 20. During purine degradation, this enzyme converts adenosine and deoxyadenosine into inosine and deoxyinosine, respectively. Mutations of ADA gene leads to lack of this enzyme, leading to an accumulation of adenosine, deoxyadenosine and the toxic metabolite deoxy-ATP. Though ADA is found in all tissues, it is highest in lymph tissues like the thymus. Its deficiency, therefore, largely impacts the immune system. Increased levels of dTAP inhibits DNA replication and leads to the death of T and B cells, which are essential to respond to infections. Thus, the absence of ADA leads to SCID,  creating a deadly vulnerability to bacterial, viral and fungal, and protozoal infections. 

Inheritance: Autosomal recessive

Epidemiology: ADA deficiency can present in the first month of life or later in infancy, childhood, adolescence, or adulthood.Large majority of cases of ADA deficiency are diagnosed in children. 

Symptoms & Signs: 

-Small, underdeveloped thymus

-Decreased feeding, poor growth and development, Failure to thrive, chronic diarrhea, pneumocystis carinii Pneumonia, and other bacterial, viral, fungal and protozoal infections 

-Associated diseases: Polyarteritis nodosa 

Diagnosis: 

Absent of very low levels of ADA, Elevated levels of adenosine and deoxyadenosine 

Treatment: 

Antibiotics to prevent and treat infections 

ADA positive red blood cell transfusions 

Bone marrow transplantation 

ADA gene therapy