SCID can be caused by a number of causes, so this particular variation is called ADA-SCID. Tandem mass spectrometry can be used for diagnosis of one of the most frequent form of SCID at a negligible cost. Recently success has been obtained in introducing the gene into lymphoid stem cells and achieving long-term expression. Adenosine deaminase deficiency, or ADA deficiency, is a rare genetic disease, that results in severe combined immunodeficiency, or SCID for short. The disorder, despite its rarity, is for several reasons considered a prime candidate for gene therapy. Enzyme replacement, now using an enzyme modified to increase the half-life and decrease immunogenicity, has been reported as successful but longer-term efficacy remains to be evaluated. Haploidentical transplants have also been successful but appear to have higher failure rates in ADA deficients than in other types of SCID. The treatment of choice is currently bone-marrow transplantation from a histocompatible related donor, if available. Most patients with ADA SCID have single base pair mutations resulting in amino acid substitutions, although a splicing mutation and a deletion have been described. The gene for ADA resides on the long arm of human chromosome 20, and both the expressed and structural gene have been isolated and characterized. Prenatal diagnosis has been made with chorionic villous samples, amniotic cells and fetal blood. The enzyme is a 40 Kd monomer that is ubiquitous, and diagnosis can be made with many cell types including erythrocytes, lymphocytes and fibroblasts. There is evidence for several mechanisms, including induction of chromosome breaks, inhibition of ribonucleotide reductase needed for normal DNA synthesis, and inactivation of SAH hydrolase needed for normal methylation reactions.
Studies indicate that these metabolites may preferentially accumulate in lymphoid cells and can interfere with lymphoid proliferation and function. Florid pathology is primarily restricted to the immune system and appears to result from accumulation of substrates (adenosine and deoxyadenosine) and metabolites (deoxy ATP).
#Adenosine deaminase scid full#
The full clinical spectrum of ADA deficiency is currently being more fully defined.
Deficiency of ADA can also result in a much later-onset, milder immunodeficiency, while lesser degrees of enzyme deficiency can result in either late-onset immunodeficiency or grossly normal immunologic function. Inherited deficiency of the purine salvage enzyme adenosine deaminase (ADA) is responsible for approximately half the cases of autosomal recessive Severe Combined Immunodeficiency (SCID). ADA-SCID is an inherited condition that mainly affects immune systems causing recurrent and opportunistic fungal, bacterial and viral infections, low white.
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