On the other hand, in the case of complete myeloperoxidase deficiency, DHR test gives abnormal results (false positive for CGD) 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 CGD 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 CGD. 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
Chronic granulomatous disease 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.
Fanconi anaemia (FA) is a rare genetic disease resulting in impaired response to DNA damage. Although it is a very rare disorder, study of this and other bone marrow failure syndromes has improved scientific understanding of the mechanisms of normal bone marrow function and development of cancer. Among those affected, the majority develop cancer, most often acute myelogenous leukemia (AML), and 90% develop aplastic anemia (the inability to produce blood cells) by age 40. About 60–75% have congenital defects, commonly short stature, abnormalities of the skin, arms, head, eyes, kidneys, and ears, and developmental disabilities. Around 75% have some form of endocrine problem, with varying degrees of severity. FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination.Treatment with androgens and hematopoietic (blood cell) growth factors can help bone marrow failure temporarily, but the long-term treatment is bone marrow transplant if a donor is available. Because of the genetic defect in DNA repair, cells from people with FA are sensitive to drugs that treat cancer by DNA crosslinking, such as mitomycin C. The typical age of death was 30 years in 2000.FA occurs in about one per 130,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa. The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. It should not be confused with Fanconi syndrome, a kidney disorder also named after Fanconi.