Test Your Knowledge of Severe Combined Immunodeficiency (SCID) Types

Classification of Severe Combined Immunodeficiency (SCID)

• SCID is a group of genetic disorders that result in the absence or dysfunction of T, B, and/or NK cells, leading to severe immune deficiency.
• X-linked SCID is caused by defects in the common gamma chain of the interleukin receptor, resulting in the inhibition of both T and NK cell development and a T−NK− phenotype. B cells counts vary from normal to high, but function is impaired.
• Autosomal recessive SCID can be caused by JAK3 or CD25 deficiency, resulting in a T−B+NK− phenotype similar to X-linked SCID.
• ADA deficiency and PNP deficiency are purine metabolism disorders that result in the accumulation of toxic metabolites, leading to a decrease in T, B, and NK cells and a T−B−NK− phenotype. ADA-SCID is more common than PNP-SCID.
• Reticular dysgenesis is a rare form of SCID caused by the defect in mitochondrial adenylate kinase 2, leading to the accumulation of toxic metabolites that affect all hematopoietic stem cells, resulting in a T−B−NK− phenotype along with granulocytopenia and deafness.
• Defects in V(D)J recombination, which affect lymphocyte antigen receptor rearrangement, result in a T−B−NK+ phenotype.
• RAG1 and RAG2 enzymes help mediate double-strand DNA breakage recombination sites, and their deficiency results in cleavage defects during V(D)J recombination. Mutations in these genes can also cause Omenn syndrome, a type of leaky SCID.
• Mutations in Artemis, DNA ligase IV, and Cernunnos/XLF genes also result in failure to resolve hairpins during V(D)J recombination, leading to a T−B−NK+ phenotype and radiosensitivity.
• Specific inhibition of T cell development can result in a T−B+NK+ phenotype.
• IL7α deficiency is a common form of SCID, as IL 7 provides survival and proliferative signals for early T cell development.
• Mutations in CD45, CD3ε, CD3δ, and Orai 1 result in an absence of T cells, while NK cells are normal. B cells can be normal or reduced.
• CORO1a gene defect leads to Coronin-1A deficiency, which is essential for T cell egression from the thymus. CORO1a deficiency results in a T−B+NK+ phenotype with the presence of the thymus.