Immunodeficiency: DiGeorge Syndrome, SCID, IgA Deficiency, MPO Deficiency & CGD

“Recurrent” is often the key word when it comes to identifying an immunodeficiency in a question stem. Anybody can get an isolated infection, but if a patient is having frequent infections that is a sign that their immune system is not functioning properly. Immunodeficient people also tend to get infections in various different locations and have infections that persist despite proper treatment. Failure to thrive (an infant that is very small for their age) is also common in immunodeficiency as these disorders are inherited and often appear during infancy. Sometimes question stems will hint at a family history of recurrent infections which points towards the genetic nature of most immunodeficiencies.



X-linked (Bruton’s) Agammaglobinemia is a rare mutation in Bruton Tyrosine Kinase which is important for the signal transduction that results in B-Cell maturation. Because maturation is inhibited only immature B-Cell Precursors are present. There is a resulting lack of germinal centers in the lymph node, because that is where B-Cells normally differentiate & proliferate.  Very low levels of circulating B-Cells are present as well as almost no antibody of any class. The lack of antibody manifests primarily as a susceptibility to encapsulated bacteria that results in pneumonia, otitis media and cellulitis in early childhood. The defect is not apparent until about 6 months of age as infants are protected for the first 6 months by their mother’s antibodies. It is an X-linked disorder and therefore is much more common in boys.

(Selective) IgA Deficiency is a common immune deficiency that results in low levels of IgA and normal levels of all other isotypes. It is inherited, but the cause is not well understood. This disorder is usually asymptomatic and many people don’t even realize they have it. IgA deficiency is often not diagnosed until a patient receives a blood transfusion and has an anaphylactic reaction to IgA in the donated blood. A small percentage of IgA deficient individuals have recurrent mucosal infections (ears, GI, respiratory…) such as Giardia infections.

DiGeorge Syndrome is an abnormal development of the 3rd and 4th pharyngeal pouches that causes an absence of the thymus and parathyroid glands. Absence of the thymus means T-Cells cannot mature and absence of the parathyroid glands cause low levels of parathyroid hormone. This congenital hypoparathyroidism leads to low calcium levels and twitching/spasms. The low levels of T-Cells leads to susceptibility for viral and candida infections. The keywords here are absent thymic shadow on chest x-ray. DiGeorge Syndrome is also associated with Truncus Arteriosus and facial abnormalities such as a cleft palate and low set ears.

Absent Thymic Shadow on Chest X-Ray DiGeorge SCID


Severe Combined Immunodeficiency (SCID) is a T-Cell deficiency COMBINED with a B-Cell deficiency. This can either be a defect in the IL-2 receptor or dysfunction the Adenosine Deaminase enzyme (adenosine builds up and is toxic to B & T Cells). There is an absent thymic shadow on the chest x-ray similar to DiGeorge, low levels of T-Cells and low levels of immunoglobulin of all isotypes.

Chronic Granulomatous Disease (CGD) is an X-linked recessive defect in NADPH Oxidase enzyme. Without functioning NADPH oxidase superoxide cannot be created within the phagosome. There is also a lack of downstream free radicals, such as peroxide and hydrochlorus acid, that superoxide can be converted to. As a result engulfed material cannot be destroyed by the phagocytes and patients are suseptible to infection by catalase positive organisms like Staph Aureus, Psuedomonas and Aspergillus. Most microorganisms are catalase negative (they don’t have their own catalase enzyme) which means the small amount of peroxide they naturally produce can be converted to HOCl by the neutrophils. This HOCl can then be used in place of superoxide to destroy phagocytized material. So even though CGD patients don’t have superoxide, they can create HOCl and kill catalase negative bacteria without much trouble. Catalase positive organisms on the other hand make their own catalase which degrades the peroxide they create and prevents this procedure. CGD patients don’t have HOCl or superoxide to fight the catalase positive bacteria and they cannot be destroyed by the phagocytes. Granulomas are formed to wall off these bacteria from the rest of the body since they cannot be degraded. These granulomas are how the disease got its name. CGD patients are/were diagnosed with a Nitroblue Tetrazolium test which is abnormal/negative (fails to turn a blue color like it should). This test is/was used primarily to differentiate CGD from the similar MPO deficiency.

Nitroblue Tetrazolium Test Chornic Granulomatous Disease MPO deficiency

Myeloperoxidase (MPO) Deficiency is a lack of Myeloperoxidase enzyme that creates HOCl (hydrochlorus acid) from peroxide. Hydrochlorus Acid is important for phagocytes because it is used to destroy phagocytosed material. Due to its near identical clinical presentation to CGD, the two disorders are sometimes differentiated by a Nitroblue Tetrozolium test which is normal or a blue color in MPO deficiency.

4 thoughts on “Immunodeficiency: DiGeorge Syndrome, SCID, IgA Deficiency, MPO Deficiency & CGD”

  1. I love that you present information in video, table, and text/paragraph format! Seeing the info presented in a variety of ways is incredibly helpful.

    1. All you really need to know for the exam is that that phrase is a big clue for SCID or DiGeorge. These diseases don’t have T Cells since there is a congenital absence of the thymus (where T cells normally mature). So No Thymus (absent on imaging) –> No T Cells –> immunodeficiency

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