Adenosine deaminase deficiency: Treatment
- Arye Rubinstein, MD
Arye Rubinstein, MD
- Professor of Pediatrics Microbiology and Immunology
- Albert Einstein College of Medicine and Montefiore Hospital Medical Center
Adenosine deaminase (ADA) deficiency (MIM 102700) is an autosomal recessive genetic disorder. In approximately 90 percent of cases, it leads to a severe combined immunodeficiency (ADA-SCID) with dysfunction of T, B, and natural killer (NK) cells (T-B-NK- SCID) that presents in the first few months of life. However, there are also a few patients with a later onset and relatively milder disease. The wide spectrum of the ADA deficiency phenotype is largely related to the variability in genetic mutations.
All patients should begin treatment as soon as the diagnosis is established [1,2]. Early intervention is critical since life-threatening opportunistic infections are not unusual in the first weeks or months of life. Furthermore, the accumulation of toxic metabolites may interfere irreversibly with the ontogenic development of the immune system.
The treatment of ADA deficiency is presented in this topic review. The pathogenesis, clinical manifestations, and diagnosis of ADA deficiency are discussed separately, as is the related combined immunodeficiency disorder, purine nucleoside phosphorylase deficiency. (See "Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis" and "Purine nucleoside phosphorylase deficiency".)
Gene therapy and hematopoietic cell transplantation (HCT) for primary immunodeficiencies are also discussed in detail separately. (See "Gene therapy for primary immunodeficiency" and "Hematopoietic cell transplantation for primary immunodeficiency".)
Exposure to contagious illnesses should be minimized as best as possible. Patients should receive prophylactic antibiotics, including Pneumocystis jirovecii (carinii) prophylaxis. Patients with adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) are at increased risk of antibiotic-induced myelotoxicity . Certain products should NOT be administered, including live vaccines or nonirradiated, cytomegalovirus (CMV)-positive blood products. Immune globulin replacement therapy, including additional respiratory syncytial virus (RSV) prophylaxis, should be given. A detailed discussion of these and other issues related to general protective measures in patients with immune deficiency is presented separately. (See "Primary immunodeficiency: Overview of management" and "Severe combined immunodeficiency (SCID): An overview".)
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- GENERAL MEASURES
- HEMATOPOIETIC CELL TRANSPLANTATION
- ENZYME REPLACEMENT THERAPY
- Exchange transfusion
- Polyethylene glycol-ADA
- - Dosing
- - Immune reconstitution
- - Long-term efficacy
- - Effect on other clinical features
- Carrier erythrocyte encapsulated ADA therapy
- GENE THERAPY
- THYMIC AND FETAL LIVER GRAFTS
- INHIBITION OF DEOXYNUCLEOSIDE KINASES
- SUMMARY AND RECOMMENDATIONS