Aurora, an 18 month old girl, is brought to the clinic because of frequent respiratory and ear infections. At first glance, you notice she has some small dilated blood vessels over the sclera of her eyes. Upon physical examination, you also realize that she has a delay in speech, as well as frequent stumbling when walking. Laboratory studies are obtained, showing a low lymphocyte count, low immunoglobulin levels, and high alpha-fetoprotein or AFP. Next comes Mathew, a 16 month old boy that’s brought to the clinic because of a skin rash that appeared on his back since infancy and won’t go away. Mathew’s mother also tells you that he has frequent spontaneous nosebleeds, and has had recurrent respiratory tract infections over the last few months. Laboratory studies are obtained, revealing that Mathew’s platelets are quite small in size and fewer than normal, while the immunoglobulins IgA and IgE are increased.
Based on the initial presentation, both cases seem to have some form of combined B- and T-cell disorder causing immunodeficiency, meaning that their immune system's ability to fight pathogens is compromised. Combined B- and T-cell disorders are characterized by defects in the development of both B and T cells, which respectively lead to impaired antibody and cellular immune responses. For your exams, the most high yield combined B- and T-cell disorders include severe combined immunodeficiency, ataxia telangiectasia, hyper IgM syndrome, and Wiskott-Aldrich syndrome.
Okay, then! Starting with severe combined immunodeficiency, or SCID for short, which is the most severe form of primary immunodeficiencies. In fact, the immune system is so dysfunctional that it’s considered almost completely absent.
Now, for your exams, remember that SCID can be caused by mutations in a variety of genes, the most common one codes for the gamma chain of the IL-2 receptor. For your exams, remember that this mutation is X-linked recessive. Okay, now, this protein is a necessary component of the IL-2 receptor, which is involved in lymphocyte maturation and activation. In SCID, the mutated gamma chain leads to the production of a defective IL-2 receptor, and thus a lack of functional mature lymphocytes.