Adenosine deaminase deficiency

Adenosine deaminase deficiency
Synonyms	ADA deficiency, ADA-SCID
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Specialty	Immunology, Genetics
Symptoms	Severe combined immunodeficiency, recurrent infections, failure to thrive
Complications	N/A
Onset	Infancy
Duration	Lifelong
Types	N/A
Causes	Mutations in the ADA gene
Risks	Family history
Diagnosis	Genetic testing, Blood test
Differential diagnosis	Other forms of severe combined immunodeficiency
Prevention	Genetic counseling
Treatment	Bone marrow transplant, Gene therapy, Enzyme replacement therapy
Medication	Pegademase
Prognosis	Variable, depends on treatment
Frequency	Rare
Deaths	N/A

A genetic disorder affecting the immune system

Adenosine deaminase deficiency (ADA deficiency) is a rare, inherited 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. Individuals with ADA deficiency are highly susceptible to infections due to the lack of functional immune cells.

Pathophysiology

Adenosine deaminase (ADA) is an enzyme involved in the purine metabolism pathway. It is responsible for the deamination of adenosine and deoxyadenosine, converting them into inosine and deoxyinosine, respectively. In individuals with ADA deficiency, mutations in the ADA gene lead to a lack of functional ADA enzyme. This results in the accumulation of toxic metabolites, such as deoxyadenosine triphosphate (dATP), which are particularly harmful to lymphocytes, the white blood cells crucial for immune function.

Clinical Presentation

The clinical manifestations of ADA deficiency typically appear in infancy. Affected infants present with recurrent infections, failure to thrive, and chronic diarrhea. Without treatment, ADA deficiency can lead to life-threatening infections and early death. Some individuals may have a later onset of symptoms, known as "delayed onset ADA deficiency," which can present in childhood or adulthood with less severe immune dysfunction.

Diagnosis

Diagnosis of ADA deficiency is based on clinical evaluation, laboratory tests, and genetic testing. Laboratory tests may reveal low levels of lymphocytes (lymphopenia) and elevated levels of toxic metabolites in the blood. Genetic testing can confirm mutations in the ADA gene.

Treatment

The primary treatment for ADA deficiency is hematopoietic stem cell transplantation (HSCT), which can restore immune function by providing the patient with healthy stem cells capable of producing functional lymphocytes. Enzyme replacement therapy (ERT) with pegylated ADA (PEG-ADA) is another treatment option, which involves regular injections of the ADA enzyme to reduce toxic metabolite levels. Gene therapy, which involves inserting a functional copy of the ADA gene into the patient's own stem cells, is an emerging treatment that has shown promise in clinical trials.

Prognosis

The prognosis for individuals with ADA deficiency has improved significantly with advances in treatment. Early diagnosis and intervention are crucial for improving outcomes. With appropriate treatment, many individuals can lead relatively normal lives, although they may require ongoing medical care and monitoring.

Related pages

• Severe combined immunodeficiency
• Hematopoietic stem cell transplantation
• Gene therapy
• Enzyme replacement therapy