ADA deficiency

ADA Deficiency

Adenosine deaminase (ADA) deficiency is a rare genetic disorder that affects the immune system. It is one of the causes of severe combined immunodeficiency (SCID), a group of disorders characterized by a severely compromised immune system. ADA deficiency is inherited in an autosomal recessive pattern and is caused by mutations in the ADA gene, which leads to a lack of the enzyme adenosine deaminase.

Pathophysiology

The ADA enzyme is crucial for the breakdown of adenosine and deoxyadenosine, which are toxic to lymphocytes if they accumulate. In individuals with ADA deficiency, the absence or malfunction of this enzyme results in the accumulation of these toxic metabolites, leading to the destruction of lymphocytes, particularly T and B cells. This destruction results in a severely compromised immune system, making individuals highly susceptible to infections.

Clinical Presentation

Patients with ADA deficiency typically present in infancy with recurrent infections, failure to thrive, and chronic diarrhea. The lack of functional T and B cells leads to an inability to mount an effective immune response. Without treatment, ADA deficiency is usually fatal within the first year of life due to overwhelming infections.

Diagnosis

Diagnosis of ADA deficiency is based on clinical presentation, family history, and laboratory tests. Blood tests can reveal low levels of lymphocytes and elevated levels of toxic metabolites. Genetic testing can confirm mutations in the ADA gene. Newborn screening programs in some regions include tests for SCID, which can detect ADA deficiency early.

Treatment

The primary treatment for ADA deficiency is hematopoietic stem cell transplantation (HSCT), which can restore immune function. Enzyme replacement therapy (ERT) with pegylated ADA (PEG-ADA) is another treatment option that can provide temporary immune function. Gene therapy, which involves inserting a functional ADA gene into the patient's own hematopoietic stem cells, has shown promise in clinical trials.

Prognosis

With early diagnosis and appropriate treatment, individuals with ADA deficiency can lead relatively normal lives. HSCT offers the potential for a cure, while ERT and gene therapy can significantly improve quality of life and reduce the risk of infections.

Also see

• Severe Combined Immunodeficiency
• Gene Therapy
• Hematopoietic Stem Cell Transplantation
• Enzyme Replacement Therapy