Myeloperoxidase deficiency

ALSO KNOWN AS: MPO deficiency; Grignashi anomaly; Alius-Grignashi anomaly

DEFINITION Myeloperoxidase deficiency is a disorder of the immune system that affects the body’s ability to kill pathogens. Myeloperoxidase is an enzyme that is located in the granules of neutrophils and in the lysosomes of monocytes and is a key component of oxygen-dependent microbial killing by these cells. A patient with myeloperoxidase deficiency has an increased risk of infections because of the reduced ability to kill some infection-causing organisms.

Risk Factors

Myeloperoxidase deficiency is an inherited disorder resulting from a variety of mutations, and no known risk factors have been associated with the disorder other than having a parent who carries a mutation. The acquired form, which is usually only temporary, has been associated with pregnancy, drugs, renal transplantation, lead toxicity, iron deficiency, and leukemias, among others factors. A 2023 study from the US National Library of Medicine indicated that inherited myeloperoxidase deficiency occurred in about 1 in 2,000 to 1 in 4,000 people in the United States and Europe. Rates in Japan appeared to be significantly lower at 1 in 55,000.

Etiology and Genetics

Myeloperoxidase is involved in the process of killing pathogens. Some white blood cells, particularly neutrophils and monocytes, can ingest pathogens via phagocytosis and use chemical methods to destroy them so that they cannot cause widespread infection. Myeloperoxidase is one of the enzymes involved in killing of pathogens. Without myeloperoxidase, a person cannot kill certain pathogens and is more prone to infections with those organisms. Most bacteria can be killed by other mechanisms, but a select group of organisms, mostly fungi, can apparently be killed only by myeloperoxidase. Patients with myeloperoxidase deficiency have increased risk of infections with these organisms.

Myeloperoxidase is an iron-containing that is the product of a single gene located on chromosome 17. The initial gene product undergoes numerous changes before becoming a functional enzyme. Mutations that affect any of these steps can result in an enzyme that is nonfunctional or has reduced activity, thus resulting in complete or partial myeloperoxidase deficiency. Several mutations have been identified, with others likely to be discovered in the future.

The inheritance of myeloperoxidase deficiency was originally described as autosomal recessive. However, since multiple mutations have been identified, researchers believe that most patients have either the same mutation on both copies of the gene (homozygotes) or a different mutation on each copy (compound heterozygotes). Patients may also have only one mutation on one copy (heterozygotes), which could result in a partial deficiency. Homozygotes and compound heterozygotes can have varying levels of deficiency as well, depending on the effect the mutation has on the enzyme.

Two types of mutations have been identified in myeloperoxidase deficiency. Several missense mutations have been identified. A is one that causes a replacement of one for another in the protein chain. Deletion mutations have also been identified. A deletion mutation is one that causes a deletion of one or more base pairs from DNA, thus affecting the final protein structure and function.

Symptoms

About half of all patients with myeloperoxidase deficiency are asymptomatic. The other half experience infections, especially fungal infections caused by certain Candida species. Patients who also have diabetes mellitus are most likely to have recurrent infections. The range of symptoms from asymptomatic to life-threatening infections is most likely related to the varying degrees of deficiency that are displayed in patients with different mutations. Myeloperoxidase deficiency patients also have an increased incidence of cancer.

Screening and Diagnosis

Because patients are often asymptomatic, myeloperoxidase deficiency often goes undiagnosed. While screening is not performed for this disorder, there are laboratory assays that detect the level of the myeloperoxidase enzyme and enzyme activity.

Treatment and Therapy

Patients with myeloperoxidase deficiency are not routinely given long-term preventive or antifungal medications. However, patients who also have diabetes mellitus are at increased risk for infections, so these patients may require drug therapy to prevent infections. Each patient case should be assessed on an individual basis to determine the need for prophylactic antimicrobial drugs.

Prevention and Outcomes

Because myeloperoxidase deficiency is an inherited disorder, there are no preventive measures that can be taken. The prognosis for patients is generally very good, with many being asymptomatic for life. Studies have shown that only 5 to 10 percent of patients acquire life-threatening infections as a result of myeloperoxidase deficiency, and most of these also have diabetes mellitus. Therefore, patients with both myeloperoxidase deficiency and diabetes mellitus should work closely with their doctors to take measures to prevent serious infections.

Bibliography

Abbas, A. K., et al. Basic Immunology: Functions and Disorders of the Immune System. St. Louis: Elsevier Health Sciences, 2008. Print.

Lichtman, M. A., et al., eds. Williams Hematology. 7th ed. New York: McGraw-Hill Medical, 2006. Print.

Nauseef, William N. “Diagnostic Assays for Myeloperoxidase Deficiency.” Neutrophil Methods and Protocols. Ed. M. T. Quinn et al. Totowa: Humana, 2007. Print.

Pahwa, Roma, Pranav Modi, and Ishwarlal Jialal. "Myeloperoxidase Deficiency." National Library of Medicine, 31 July 2023, www.ncbi.nlm.nih.gov/books/NBK470278/. Accessed 9 Sept. 2024.

Rich, Robert R., ed. Clinical Immunology: Principles and Practice. 4th ed. Oxford: Elsevier, 2013. Print.

Schaefer, G. Bradley, and James N. Thompson Jr. Medical Genetics: An Integrated Approach. New York: McGraw-Hill, 2014. Print.

Turgeon, Mary Louise. Immunology and Serology in Laboratory Medicine. 5th ed. St. Louis: Mosby, 2014. Print.