Autosomal recessive SCID includes the following types of defeciencies:-
a) Adenosine Deaminase Deficiency
An absence of the enzyme adenosine deaminase (ADA) has been observed approximately 15% of patients with SCID[6].ADA is an essential enzyme in our body and it helps in various metabolic processes of different cells.of all the cells it is most essential for T-cell functioning.when this enzyme is deficient or absent then it leads to deposition of adenosine,2’-deoxyadenosine, and 2’-o-methyladenosine[6] . These compounds are harmful for the lymphocytes and they die off.in this type of scid have the lowest total lymphocyte counts of all and T,B and NK-lymphocyte counts are all very low.[3]
b) Janus kinase 3 deficiency
This type of SCID is caused due to a mutation in chromosome number 19.this chromosome harbours the gene that encodes for an enzyme essential to lymphocytes and is called Janus Kinase 3 (Jak3).patients with this type of SCID are in a way similar with all other types while considering susceptibility to infection .they have an elevated percentage of B-lymphocyte and low percentage of T and NK cells.[6]
c) Intelukin-7 receptor α-chain deficiency
IL-7Ra deficiency is the 3rd most common cause of SCID accounting for 11 percent of SCID cases.”[3].Both the sexes can be affected. Often seen, the mutations in the gene for IL-7Rα on chromosome 5 also leads to SCID. In this type of deficiency of a chain of IL-7Rα receptor, infants are shown to have B-cell and NK cells but no T-cell. This results into non functioning of the B-cell which depends on T-cell for activation.
d) Recombinase-activating gene (RAG1 or RAG2) deficiencies
" Infants with autosomal recessive SCID caused by mutations in recombinase activating genes, RAG1 and RAG2, resemble all others in their infection susceptibility and complete absence of T- or B-cell function. They lack both B and T lymphocytes and have primarily NK cells in their circulation (T -B-NK + SCID). This particular phenotype suggested a possible problem with their antigen receptor genes and led to the discovery of mutations in RAG1 and RAG2 in some (but not all) such infants with SCID. These genes, on chromosome 11p13, encode proteins necessary for somatic rearrangement of antigen receptor genes on T and B cells. The proteins recognize recombination signal sequences and introduce a DNA double-stranded break, permitting V, D, and J gene rearrangements. RAG1 or RAG2 mutations result in a functional inability to form antigen receptors through genetic recombination. "[6]
e) CD45 deficiency
It is a molecular type of defect which involves a mutation in the gene encoding the common leukocyte surface protein CD45.This hematopoietic cell-specific transmembrane protein tyrosine phosphatise functions to regulate Src kinases required for T- and B- cell antigen receptor signal transduction.[6]
f) CD3 chain deficiency
Three other forms of SCID are due to mutations in the genes that encode three of the individual protein chains that make up another component of the T-cell receptor complex, CD3. These SCID causing gene mutations result in deficiencies of CDδ, ε or ζ chains.[3]
g) Deficiencies of the Artemis gene
This cause of SCID is mutation on chromosome 10p called Artemis.[we paul].this leads to the deficiency of V(D)J recombination /DNA repair factor .this deficiency results into an inability to repair DNA after double stranded cuts have been made by RAG1 or RAG2 gene products in rearranging antigen receptor genes from there germline configuration. This defects results in generation of another form of T-B-NK+ SCID, also called as Athabascan SCID.[6] Also there is an increased radiation sensitivity of both skin fibroblast and bone marrow cells of persons affected with this type of SCID.[6]
