When<unk>  <unk>  is suspected, neutrophil-function testing should be carried out, and positive findings should be confirmed by genotyping. The p47phox mutation is due to a pseudogene conversion, hence it may not be detectable by standard sequencing; in these cases, an immunoblot or gene dose determination may be needed to confirm p47phox deficiency. Infections caused by the pathogens commonly associated with<unk>  should prompt functional or genetic screening; neonatal or early postnatal screening of potentially affected children is essential with a family history of<unk> . Neutrophil function tests: These include nitroblue tetrazolium (NBT) reduction test, dihydrorhodamine (DHR) 123 test, direct measurement of superoxide production, cytochrome c reduction assay, and chemiluminescence. DHR test is usually preferred because it is easy to use, objective, and it is able to distinguish between X-linked and autosomal forms of<unk> ; furthermore, it allows to detect gp91phox carriers. * The nitroblue-tetrazolium (NBT) test is the original and most widely known test for<unk> . It is negative in<unk> , meaning that it does not turn blue. The higher the blue score, the better the cell is at producing reactive oxygen species. This test depends upon the direct reduction of NBT to the insoluble blue compound formazan by superoxide which is produced by normal peripheral blood neutrophils stimulated in vitro; NADPH oxidase catalyzes the aforementioned reaction and NADPH is oxidized in the same reaction. This test is simple to perform and gives rapid results but only tells whether or not there is a problem with the PHOX enzymes, not how much they are affected. * Dihydrorhodamine (DHR) 123 test: In this test the respiratory burst of the neutrophils is stimulated with phorbol myristate acetate (PMA), resulting in oxidation of dihydrorhodamine 123 (nonfluorescent derivative of rhodamine) to rhodamine 123 (green fluorescent compound), which can be measured by flow cytometry. This test is abnormal in patients with<unk>  (i.e., there is no shift in fluorescence with stimulation). Moreover, its quantitative nature allows to differentiate oxidase-positive from oxidase-negative phagocyte subpopulations in<unk>  carriers and identify deficiencies in gp91phox and p47phox. Modest residual production of reactive oxygen intermediates (ROI) as assessed by DHR 123 test, is associated with significantly less severe illness and a greater likelihood of long-term survival than patients with little residual ROI production. On the other hand, in the case of complete myeloperoxidase deficiency, DHR test gives abnormal results (false positive for<unk>  because the DHR signal yielded by flow cytometry depends on intact NADPH oxidase activity as well as the presence of a myeloperoxidase (MPO); however, NBT test demonstrates normal production of superoxide. Genetic testing: Once<unk>  has been diagnosed based on abnormal neutrophil function tests, genetic testing should go next. As mentioned above, p47phox defect is usually difficult to identify genetically because it is caused by pseudogene conversion and may be missed in typical sequencing studies; in this case, immunoblotting or flow cytometry can show absence of protein. Prenatal testing: It is particularly useful when a family member has already been diagnosed with<unk> . This test may be performed by analysis of NADPH oxidase activity of neutrophils from fetal blood. Samples from amniotic fluid or chorionic villi provides an earlier and more reliable diagnosis for families at risk. Classification<unk>  is the name for a genetically heterogeneous group of immunodeficiencies. The core defect is a failure of phagocytic cells to kill organisms that they have engulfed because of defects in a system of enzymes that produce free radicals and other toxic small molecules. There are several types, including: * X-linked<unk>  <unk>  * autosomal recessive cytochrome b-negative<unk>  * autosomal recessive cytochrome b-positive<unk>  type I * autosomal recessive cytochrome b-positive<unk>  type II * atypical<unk><unk>
Chronic granulomatous disease
Common variable immunodeficiency
Wiskott–Aldrich syndrome
Severe combined immunodeficiency
Primary immunodeficiency
X-linked agammaglobulinemia
Selective immunoglobulin A deficiency
SAPHO syndrome