![]() ADA deficiency has also been found in less severely affected patients with delayed or late/adult onset of immune deficiency ( 3, 5, 6, 7, 8, 9, 10). A marked increase in the level of dAdo nucleotides (dAXP) in erythrocytes is characteristic of ADA-deficient SCID. Inherited deficiency of ADA causes one of the autosomal recessive forms of severe combined immunodeficiency (SCID) ( 3), which is thought to result from accumulation of toxic metabolites of ADA substrates in lymphoid cells ( 4). The 32-kb ADA gene consists of 12 exons located on chromosome 20q1-2 ( 1, 2). These results further define the threshold level of ADA activity necessary for sustaining immune function.Īdenosine deaminase (ADA 3 EC 3.5.4.4), an enzyme of the purine salvage pathway, catalyzes the conversion of adenosine and 2′-deoxyadenosine (dAdo) to inosine and 2′-deoxyinosine, respectively. Immunoblotting suggested that this lability was due to denaturation rather than to degradation of the mutant protein. ADA activity in EBV-LCL extracts of the paradoxical carriers was much more labile than ADA from normal EBV-LCL. Expression of cloned mutant ADA cDNAs in an ADA-deletion strain of Escherichia coli indicated that the novel mutations G239S and M310T were responsible for the residual ADA activity. Each of these carriers possessed two mutated ADA alleles. ![]() ADA activity in EBV-lymphoblastoid cell lines (LCL) and T cell lines established from these carriers was 10–20% of normal. Unexpectedly, healthy first-degree relatives of two unrelated ADA-deficient severe combined immunodeficient patients (mother and brother in family I mother in family II) had only 1–2% of normal ADA activity in PBMC, lower than has previously been found in PBMC of healthy individuals with so-called “partial ADA deficiency.” The level of deoxyadenosine nucleotides in erythrocytes of these paradoxical carriers was slightly elevated, but much lower than levels found in immunodeficient patients with ADA deficiency. In general, ADA activity in cells of carriers is approximately half-normal. Adenosine deaminase (ADA) deficiency causes an autosomal recessive form of severe combined immunodeficiency and also less severe phenotypes, depending to a large degree on genotype.
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