![]() Babies with this type of SCID can have the lowest total lymphocyte counts of all because T, B, and NK lymphocyte counts are all very low. ADA deficiency is the second most common cause of SCID, accounting for about 15% of cases. The absence of this enzyme leads to an accumulation of toxic metabolic byproducts within lymphocytes that cause the cells to die. ADA is essential for the metabolic function of a variety of body cells but especially T cells. Adenosine Deaminase DeficiencyĪnother common type of SCID is caused by mutations in a gene that encodes an enzyme called adenosine deaminase (ADA). RAG1 and RAG2 mutations are seen in 40% of those with leaky SCID and about 19% of those with SCID overall. Babies with this type of SCID will present with low or absent T and B cells, but typically have normal or high NK cells. RAG1 and RAG2 are enzymes critical to development of T and B cells, but not NK cells. With the advent of newborn screening, improved access to genetic testing and recognition of leaky SCID as a clinical entity, there has been increased diagnosis of SCID caused by autosomal recessive mutations in Recombinase Activating Gene 1 and 2 (RAG1 and RAG2). Deficiency of Recombinase Activating Gene 1 and 2 (See Inheritance Chapter.) Only males have this type of SCID, but females may carry the gene and have a 1 in 2 chance (50%) of passing it on to each son as well as a 1 in 2 chance of passing the carrier state on to each daughter. (See The Immune System and Primary Immunodeficiency Diseases Chapter.) This deficiency is inherited as an X-linked recessive trait. Despite the presence of B lymphocytes, there is no B lymphocyte function, since the B cells have abnormal receptors for growth factors on their cell surfaces. Changes in this gene result in very low T lymphocyte and NK lymphocyte numbers, but the B lymphocyte count is normal or high (a so-called T-, B+, NK- phenotype). This component is referred to as the common gamma chain (γc). The most common form of SCID, affecting nearly 30% of all cases, is due to a mutation in a gene on the X chromosome that encodes a component (or chain) called IL2RG shared by the T cell growth factor receptor and other growth factor receptors. Deficiency of the Common Gamma Chain of the T Cell Receptor While these patients can be diagnosed in infancy, particularly if SCID newborn screening is available, many are diagnosed later in life. In these patients, there are low numbers of T cells with reduced but not absent function. Recently, leaky or atypical (hypomorphic) SCID was described. Although they vary with respect to the genetic type that causes the immunodeficiency, some of their laboratory findings and their pattern of inheritance, these infants all have an absence of T cells and severe deficiencies in both T cell and B cell function. There are currently at least thirteen different genes that, when mutated (changed), cause SCID. These defects lead to extreme susceptibility to serious infections. SCID is a rare and fatal syndrome of diverse genetic causes in which there is combined absence of T lymphocyte and B lymphocyte function and in many cases also natural killer (NK) lymphocyte function. Fortunately, effective treatments, such as hematopoietic stem cell transplantation (bone marrow transplant), exist that can treat the disorder, and the future holds the promise of gene therapy for some types. This condition is generally considered to be one of the most serious forms of PI. These defects lead to extreme susceptibility to very serious infections. ![]() There are at least 13 different genetic defects that can cause SCID. SCID is fatal without a stem cell transplant or corrective gene therapy. ![]() Severe Combined Immunodeficiency (SCID, pronounced “skid”) is a serious primary immunodeficiency disease (PI) in which there is combined absence of T lymphocyte and B lymphocyte function. ![]()
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