What is the cause of SCID?

[MudPhud20XX]

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So Kaplan Immunology explains that SCID (Severe Combined Immunodeficiency) is due to the molecular defect of rag genes, whereas FA explains that ADA (Adenosine Deaminase Deficiency) is the most common cause for SCID.

I am guessing that these two causes are two different underlying mechanisms right?

Also, I've always thought it was strange that ADA would lead to SCID. I mean ADA messes up with DNA synthesis that leads to low count of lymphocytes among many things that can go wrong? Perhaps this is beyond the scope of USMLE, but I am just curious. Anyone has a clue?

Many thanks in advance.

 

[tranquilo]

There are several causes of SCID. Most common cause is a defect in the gamma chain in the IL 2 receptor gene (X-linked). Second most common is a defect in ADA (autosomal dominant). Mutations in RAG1, RAG2 are rare causes of SCID.
I think defects in ADA causes accumulation of toxic metabolites that impede T cell maturation. I hope this gets you going.

 

[notbobtrustme]

Also, I've always thought it was strange that ADA would lead to SCID. I mean ADA messes up with DNA synthesis that leads to low count of lymphocytes among many things that can go wrong? Perhaps this is beyond the scope of USMLE, but I am just curious. Anyone has a clue?

it causes ATP to build up which in turns builds up dATP which shuts off ribonucleotide reductase (remember dATP shuts of all nucleotide synthesis, while the other deoxy nucleotides shut off the synthesis of themselves, eg dGTP shuts off synthesis of dGTP). With RNR shutdown, cells that divide a large number of times (eg lymphocytes) don't proliferate properly, causing SCID.

 

[MudPhud20XX]

Thanks a lot guys! I really appreciate it.