Avoid all live viral vaccines (rotavirus, varicella, MMR, BCG) Once a patient with suspected SCID is identified, several immediate management steps must be implemented: In both cases, circulating T-cells have a predominantly memory phenotype (CD45RO) and proliferation in response to mitogens is very low.ĩ. T-cell numbers can occasionally be normal if maternal T-cell engraftment has occurred or if a hypomorphic (leaky) SCID mutation allows for development of residual autoreactive T-cells that undergo clonal expansion and invade tissues such as the skin or liver (Omenns syndrome). This particular type of SCID can be treated with enzyme replacement therapy (PEG-ADA).Ĩ. Deficiency of ADA results in the accumulation metabolites that are toxic to all types of lymphocytes. Adenosine Deaminase (ADA) deficiency accounts for 20% of all SCID cases and results in a T-B-NK- SCID phenotype. JAK3 deficiency (10% of all cases) results in an identical phenotype because JAK3 is a signaling molecule immediately downstream from the common gamma chain.ħ. This form of SCID results in a T-B+NK- phenotype because the impaired signaling impairs T-cell and NK cell development, but it does not affect B-cell development. X-linked SCID is caused by mutations in the common gamma chain of the IL-2 receptor and accounts for 50% of all SCID cases. T-B+NK+ SCID, T-B+NK- SCID, T-B-NK+ SCID, and T-B-NK- SCID are the 4 major categories.Ħ. Classification of the different types of SCID based on the pattern of lymphocyte subpopulation depression is a useful strategy for determining the genetic defect. T-cell proliferation to mitogens is markedly decreased (<10% of control).ĥ. B-cell and NK-cell numbers may or may not be decreased depending on the type of SCID. Lymphocyte subset analysis reveals low T-cell numbers. Lymphopenia (95% have an ALC < 2800 cells/mm3) is a laboratory hallmark of SCID. The thymic shadow is often absent in infants with SCID.Ĥ. Clinically patients present early in infancy (before 6 months of age) with chronic candidiasis, protracted diarrhea and FTT, Pneumocystis jiroveci pneumonia, and chronic respiratory virus infections. Thus, patients have complete absence of cell-mediated and antibody-mediated immunity.ģ. Although some mutations allow for B-cell development to occur, B-cell function is invariably impaired due to the absence of T-cell co-stimulatory signaling. Although there are many different causes of SCID (more than 30 have been described to date), the unifying feature shared by all types is a complete absence of T-cell development. The overall incidence is 1 in 50,000 newborns.Ģ. Severe Combined Immunodeficiency (SCID) is one of the most serious primary immunodeficiencies because it is often fatal in the first year of life without proper diagnosis and therapeutic intervention.
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