ADA-deficient SCID is characterized by severe lymphocytopaenia affecting T-and B-lymphocytes and NK cells, but, because of the ubiquitous nature of the enzyme, non-immunological manifestations are also observed, including neurodevelopmental deficits, sensorineural deafness and skeletal abnormalities. Absent or impaired ADA function leads to the accumulation of the toxic metabolites adenosine, 2’deoxyadenosine and deoxyadenosine triphosphate (dATP). This article reviews the biology, clinical presentation, diagnosis and treatment of ADA-deficiency.Īdenosine deaminase (ADA) is a key enzyme of the purine salvage pathways and deficiency caused by mutations in the ADA gene results in one of the more common causes of autosomal recessive severe combined immunodeficiency (SCID), accounting for approximately 10–15% of cases in outbred populations. More recently, the use of gene addition techniques to correct the genetic defect in autologous haematopoietic stem cells treatment has demonstrated immunological and clinical efficacy. Hematopoietic stem cell transplant has long been established as the treatment of choice, particularly where a matched sibling or well matched unrelated donor is available. Initial treatment with enzyme replacement therapy may alleviate acute symptoms and enable partial immunological reconstitution, but treatment is life-long, immune reconstitution is incomplete, and the reconstituted immune system may nullify the effects of the enzyme replacement. Three treatment options are currently available. Affected patients present in early infancy, usually with persistent infection, or with pulmonary insufficiency. Whilst most notable affects are on lymphocytes, other manifestations include skeletal abnormalities, neurodevelopmental affects and pulmonary manifestations associated with pulmonary-alveolar proteinosis. Adenosine deaminase (ADA) deficiency leads to an accumulation of toxic purine degradation by-products, most potently affecting lymphocytes, leading to adenosine deaminase-deficient severe combined immunodeficiency.
0 kommentar(er)
