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At a glance

Severe Combined Immunodeficiency (SCID) is a heterogeneous group of syndromes related to alterations of distinct genes that cause abnormalities in the maturation and/or function of T, B, and/or NK cells. It is generally considered to be the most serious of the primary immunodeficiency diseases. Without intervention, death in children occurs by age 2 years.

Synonyms

SCIDX Syndrome; X-SCID Syndrome; Janus Associated Kinase 3 Deficiency; JAK 3 Deficiency; Adenosine Deaminase Deficiency; ADA Deficiency; Purine Nucleoside Phosphorylase Deficiency; PNP Deficiency; Bare Lymphocyte Syndrome; IL-2 Deficiency; ZAP-70 Protein Tyrosine Kinase Deficiency; ZAP-70 PTK Deficiency; Reticular Dysgenesia; Omenn Syndrome.

Classification

Conventionally classified according either to the main pathways affected by the molecular defect or on the basis of the specific immunologic phenotype related to that genetic defect. They consists of the following:

  • T cell deficient but normal B cell (T–B+) SCID

  • T cell and B cell deficient (T–B–) SCID

  • NK cells (NK+ or NK–): Characterized by either the presence or absence of the cells. This condition accounts for further subdivisions based on the presence of these cells.

Incidence

1:100,000 live births. Higher incidence recently reported (1:50,000-1:75,000 live births), probably because of better identification of affected subjects.

Genetic inheritance

Either X-linked (SCIDX; gene mapped to Xq13) or autosomal recessive (s.a. Janus-associated kinase 3 [JAK3] deficiency or adenosine deaminase [ADA] deficiency).

Pathophysiology

The pathophysiology and molecular biology vary according to the type of immunodeficiency. However, the lack of T- and B-cell function is the common endpoint in all forms of SCIDS.

  • X-Linked Form: X-SCID lack of IL2RG function results in near-complete absence of T and natural killer (NK) lymphocytes and nonfunctional B lymphocytes.

  • Janus-Associated Kinase 3 (JAK3) Deficiency: JAK3 is a protein tyrosine kinase (PTK) that associates with the common gamma chain of the IL receptors. Lymphopenia occurs primarily from the absence of T cells (CD3+) and NK cells. Normal or high levels of B cells occur, which do not make functional antibodies.

  • Adenosine Deaminase (ADA) Deficiency: Lymphopenia occurs from the death of T and B cells secondary to the accumulation of toxic metabolites in the purine salvage pathway. Functional antibodies are decreased or absent.

  • Purine Nucleoside Phosphorylase (PNP) Deficiency: Same as ADA deficiency with circulating B cells normal in number. B-cell function is poor, as evidenced by the lack of antibody formation.

  • Bare Lymphocyte Syndrome: This is a deficiency of major histocompatibility complex (MHC). The lymphocyte count is normal or mildly reduced, the CD4+ are decreased, and the CD8+ are normal or mildly increased. The B-cell numbers are normal or mildly decreased, but the ability to make antibodies is decreased.

  • IL-2 Deficiency: The exact molecular defect is unknown, but it is often associated with other cytokine production defects. Normal numbers of T cells exist ...

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