Myeloperoxidase deficiency

Myeloperoxidase deficiency is an autosomal recessive genetic disorder featuring deficiency, either in quantity or of function, of myeloperoxidase, a peroxidase enzyme expressed by neutrophil granulocytes. It is classified as a primary immunodeficiency disorder, and is caused by a mutation in the myeloperoxidase gene on chromosome 17q23. Between 1:1000 and 1:4000 of people in the United States and Europe are myeloperoxidase-deficient. It can appear similar to chronic granulomatous disease on some screening tests.
Pathophysiology.
In a person’s innate immune system, cells such as neutrophils and macrophages remove bacteria from the body by phagocytizing them. Once engulfed, the phagocytic cells must then degrade the captured bacteria, which is done via reactive oxygen species produced by the cell’s respiratory burst. One of these reactive oxygen species is hypochlorite, which is created by the myeloperoxidase-catalyzed conversion of hydrogen peroxide and chlorine ions. In a patient with MPO deficiency, the reaction cannot be catalyzed and hypochlorite will not be produced, rendering the neutrophils less capable of destroying certain bacterial and fungal species.
Presentation.
MPO deficiency classically presents with immune deficiency. Due to the decrease in reactive oxygen species, people with MPO may experience an increase in recurrent fungal infections, particularly candida albicans. However, the majority of MPO-deficient patients do not display any significant tendencies towards chronic infections from most other bacteria, perhaps due to increased activity in other aspects of the innate immune system, which compensate for the lack of HClO.
Diagnosis.
Myeloperoxidase deficiency can be diagnosed via flow cytometry or cytochemical stains.
Notably, MPO deficiency can present a false positive in the diagnosis of chronic granulomatous disease via DHR test. Although the two disorders are similar in that both interfere with the granulocyte’s ability to produce reactive oxygen species, CGD is caused by defects in the enzyme NADPH oxidase. NADPH oxidase-specific protein flow assays can be used to differentiate MPO deficiency from CGD. In addition, neutrophils which are MPO- but not NADPH oxidase-deficient will still turn blue in a normal nitro blue tetrazolium test because they still have NADPH oxidase activity, but do not form HClO (bleach) due to their lack of myeloperoxidase activity. This is in contrast to chronic granulomatous disease, in which the NBT test is 'negative' due to the lack of NADPH oxidase activity (positive test result means neutrophils turn blue, negative means nitroblue tetrazolium remains yellow).
Treatment.
MPO deficiency can technically be treated by the transplant of hemipotent stem cells from an unaffected patient to an MPO-deficient one. However, the symptoms of MPO deficiency are not severe and possibly unnoticeable, as determined by the realization in 1981 that far more of the population is MPO deficient than previously suspected. Therefore, treatment is usually unnecessary.
The fungal infections which may occur as a result of MPO deficiency may be treated with antibiotics.