Hematology

Myeloperoxidase deficiency

Myeloperoxidase deficiency

What every physician needs to know:

Myeloperoxidase (MPO) catalyzes the conversion of hydrogen peroxide to hypohalous acid (bleach in the neutrophil where the halide is chloride). MPO deficiency is the most common phagocyte defect, but causes very little in the way of clinical disease.

Are you sure your patient has myeloperoxidase deficiency? What should you expect to find?

MPO deficiency is only occasionally suspected, and then usually because of Candida infection. The diagnosis is made by immunohistochemical staining of neutrophils for MPO activity, which is abundant in normal neutrophils and eosinophils.

Beware of other conditions that can mimic myeloperoxidase deficiency:

MPO deficiency causes an abnormality in neutrophil oxidation of dihydrorhodamine (DHR), the dye used in the flow cytometric diagnosis of chronic granulomatous disease (CGD). This is important to keep in mind, since the standard test for CGD is now DHR, and MPO deficiency will give a false diagnosis of CGD.

The way to confirm the accuracy of the DHR, in cases where the diagnosis of CGD seems incorrect, is to use a second assay of superoxide production (abnormal in CGD), such as nitroblue tetrazolium reduction or ferricytochrome c reduction. Alternatively, one can stain the neutrophils for MPO expression, which is normal in CGD and absent in complete MPO deficiency.

Which individuals are most at risk for developing myeloperoxidase deficiency:

MPO deficiency is genetically determined.

Infections in MPO deficiency are almost exclusively seen in the setting of diabetes mellitus, for reasons still poorly understood.

What laboratory studies should you order to help make the diagnosis and how should you interpret the results?

Immunohistochemistry of neutrophils for MPO activity is the most available diagnostic test and performed by most hematopathology laboratories as a marker of neutrophils in bone marrow sections. Molecular testing of MPO sequence is available as well.

What imaging studies (if any) will be helpful in making or excluding the diagnosis of disease Myeloperoxidase Deficiency?

None.

If you decide the patient has myeloperoxidase deficiency, what therapies should you initiate immediately?

Management of infections as they develop. Prophylaxis has not generally been needed.

More definitive therapies?

Infection management.

What other therapies are helpful for reducing complications?

Control of comorbid conditions such as diabetes mellitus.

What should you tell the patient and the family about prognosis?

Benign except for occasional Candida infections. These almost always respond appropriately to treatment.

What if scenarios.

N/A

Pathophysiology

Neutrophil superoxide is formed by oxidation of nicotinamide adenine dinucleotide phosphate (NADPH) performed by the NADPH oxidase enzyme complex. Superoxide is converted to hydrogen peroxide by superoxide dismutase and then hydrogen peroxide is converted to hypohalous acid or bleach by MPO. MPO deficiency has a profound effect on the ability of neutrophils to kill Candida in vitro, but the in vivo consequences are quite modest, if any. This may reflect the strong mucocutaneous barrier that keeps Candida outside the body, at least until breached by intravenous catheters, surgery, or chemotherapy-induced mucositis.

What other clinical manifestations may help me to diagnose myeloperoxidase deficiency?

Diabetes, previous severe Candida infections.

Normal physical examination.

What other additional laboratory studies may be ordered?

Immunohistochemistry, flow cytometry, DNA sequencing.

What’s the evidence?

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