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Myeloperoxidase Deficiency Clinical Presentation

  • Author: Maureen M Petersen, MD; Chief Editor: Harumi Jyonouchi, MD  more...
Updated: Nov 17, 2014


See the list below:

  • Recurrent infections
    • Most individuals with partial or total myeloperoxidase (MPO) deficiency have no increased frequency of infections, probably because MPO-independent mechanisms in the polymorphonuclear leukocytes (PMNs) can take over. In general, it is considered a relatively benign immunodeficiency and was removed from the Classification of Primary Immunodeficiency Disease by the Primary Immunodeficiency Disease Classification Committee of the International Union of the Immunologic Societies in 2005.
    • Severe infections are uncommon, occurring in fewer than 5% of patients with MPO deficiency. If infectious disease occurs, it is usually a fungal infection (particularly candidal, such as C albicans or C tropicalis) that occurs in a patient who also has diabetes mellitus. Patients without diabetes mellitus rarely have problems, although the reason for this is unknown. Possibly, MPO deficiency becomes clinically significant only in the presence of an additional defect in the host defense, or perhaps the MPO-independent system is defective in some patients with diabetes mellitus.
    • Physicians should entertain the diagnosis of MPO deficiency in cases of invasive fungal infection in a patient with no known predisposing immune defects (eg, chemotherapy, corticosteroid treatment) or in a patient with concomitant diabetes mellitus. Some consider peroxidase staining of the peripheral blood smear to be part of the complete evaluation of a patient with a suspected immunodeficiency.
  • Increased incidence of malignancy
    • A strong association between total MPO deficiency and malignancies has been reported by several independent investigators. In vitro, MPO-deficient neutrophils have decreased destruction of malignant cells demonstrating that the MPO system plays a central role in tumor surveillance.[8]
    • MPO is released from neutrophils in lung tissue in response to pulmonary insult including damage secondary to tobacco smoke exposure. MPO has been shown to convert the metabolites of benzo[a]pyrene from tobacco smoke into a highly reactive carcinogen. Researchers have demonstrated that decreased MPO can decrease lung cancer risk.[11]


See the list below:

  • Hereditary cases can be caused by a number of mutations, including R569W, Y173C, M251T, G501S, and R499C.
    • R569W: This is the most common defect identified to date. Tryptophan is substituted for arginine at codon 569. Tryptophan cannot form electrostatic bonds. Most patients described have been compound heterozygotes, but one has been homozygous for this mutation. The mutation results in a maturational arrest at the stage of apopro-MPO that is unprocessed, enzymatically inactive, and undelivered to the azurophilic granules.[12]
    • Y173C: Cysteine is substituted for tyrosine at codon 173. This leads to an additional site for intramolecular disulfide bonds, which presumably leads to abnormal folding of the protein. Apopro-MPO is converted into pro-MPO, which is malfolded. This malfolded pro-MPO seems to be sequestered by calnexin (a molecular chaperone) and retained in the endoplasmic reticulum. The trapped precursor then undergoes degradation in the endoplasmic reticulum. Pro-MPO is prevented from entering the secretory pathway and cannot proceed to become mature MPO in the azurophilic granules. Therefore, MPO deficiency resulting from this mutation occurs because of an abnormality of protein folding. Interestingly, abnormalities in protein folding have also been described in cystic fibrosis and protein C deficiency.
    • M251T: In this defect, mature subunits are formed, but their enzymatic activity is markedly low.
    • G501S: This mutation is a missense mutation within part of the heme-binding pocket. It has been identified in a Japanese patient with complete MPO deficiency.[13]
    • R499C: This mutation is a nonsynonymous mutation that results in an arginine to cysteine substitution in the exon 9 coding region. The mutation was identified in a Japanese patient with complete MPO deficiency. Further genetic analysis revealed mRNA was transcribed into an appropriate peptide sequence, but no MPO protein was evident on Western blot findings.[14]
  • As time goes on and more cases are analyzed, more mutations are being identified. Some pretranslational defects have been described that could be caused by mutations in the regulatory portion of the MPO gene or by the presence of mutations in other genes involved in the regulation of the MPO gene.
  • Acquired MPO deficiency is less common than the hereditary form. This condition can be transient. The enzyme defect is corrected when the underlying condition has resolved. In most cases of acquired deficiency, the deficiency is partial and affects only a proportion of neutrophils (see Pathophysiology).
Contributor Information and Disclosures

Maureen M Petersen, MD Staff Physician in Allergy and Immunology, Walter Reed National Military Medical Center; National Capital Consortium Transitional Year Program Director; Assistant Professor of Pediatrics and Assistant Professor of Medicine, Uniformed Services University of the Health Sciences

Maureen M Petersen, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma and Immunology, American Thoracic Society, Clinical Immunology Society

Disclosure: Nothing to disclose.


Cecilia P Mikita, MD, MPH Associate Program Director, Allergy-Immunology Fellowship, Associate Professor of Pediatrics and Medicine, Uniformed Services University of the Health Sciences; Staff Allergist/Immunologist, Walter Reed National Military Medical Center

Cecilia P Mikita, MD, MPH is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

David J Valacer, MD 

David J Valacer, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association for the Advancement of Science, American Thoracic Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Chief Editor

Harumi Jyonouchi, MD Faculty, Division of Allergy/Immunology and Infectious Diseases, Department of Pediatrics, Saint Peter's University Hospital

Harumi Jyonouchi, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Academy of Pediatrics, American Association of Immunologists, American Medical Association, Clinical Immunology Society, New York Academy of Sciences, Society for Experimental Biology and Medicine, Society for Pediatric Research, Society for Mucosal Immunology

Disclosure: Nothing to disclose.

Additional Contributors

C Lucy Park, MD Chief, Division of Allergy, Immunology, and Pulmonology, Associate Professor, Department of Pediatrics, University of Illinois at Chicago College of Medicine

C Lucy Park, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, Chicago Medical Society, American Medical Association, Clinical Immunology Society, Illinois State Medical Society

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Javed Sheikh, MD to the development and writing of this article.

  1. Dale DC, Boxer L, Liles WC. The phagocytes: neutrophils and monocytes. Blood. Aug 2008. 112:935-945. [Medline].

  2. Klebanoff SJ, Kettle AJ, Rosen H, Winterbourn CC, Nauseef WM. Myeloperoxidase: a front-line defender against phagocytosed microorganisms. J Leukoc Biol. 2012 Oct 11. [Medline].

  3. Stefanescu A, Braun S, Ndrepepa G, et al. Prognostic value of plasma myeloperoxidase concentration in patients with stable coronary artery disease. Am Heart J. Feb 2008. 155:356-360. [Medline].

  4. Kutter D, Devaquet P, Vanderstocken G, et al. Consequences of total and subtotal myeloperoxidase deficiency: risk or benefit?. Acta Haematol. 2000. 104(1):10-5. [Medline].

  5. Rudolph TK, Wipper S, Reiter B, Rudolph V, Coym A, Detter C, et al. Myeloperoxidase deficiency preserves vasomotor function in humans. Eur Heart J. 2012 Jul. 33(13):1625-34. [Medline]. [Full Text].

  6. Nauseef WM. Insights into myeloperoxidase biosynthesis from its inherited deficiency. J Mol Med. 1998 Sep. 76(10):661-8. [Medline].

  7. Nauseef WM. Lessons from MPO deficiency about functionally important structural features. Jpn J Infect Dis. 2004 Oct. 57(5):S4-5. [Medline].

  8. Lanza F. Clinical manifestation of myeloperoxidase deficiency. J Mol Med. 1998 Sep. 76(10):676-81. [Medline].

  9. Kutter D. Prevalence of myeloperoxidase deficiency: population studies using Bayer-Technicon automated hematology. J Mol Med. 1998 Sep. 76(10):669-75. [Medline].

  10. Nunoi H, Kohi F, Kajiwara H, Suzuki K. Prevalence of inherited myeloperoxidase deficiency in Japan. Microbiol Immunol. 2003. 47(7):527-31. [Medline].

  11. Taioli E, Benhamou S, Bouchardy C, et al. Myeloperoxidase G463A polymorphism and lung cancer: a HuGE genetic susceptibility to environmental carcinogens pooled analysis. Genet Med. Feb 2007. 9:67-73. [Medline].

  12. Nauseef WM, Cogley M, and McCormick S. Effect of the R569W missense mutation on the bio-synthesis of myeloperoxidase. J Biol Chem. Apr 1996. 271:9546-9549. [Medline].

  13. Ohashi YY, Kameoka Y, Persad AS, et al. Novel missense mutation found in a Japanese patient with myeloperoxidase deficiency. Gene. 2004 Mar 3. 327(2):195-200. [Medline].

  14. Persad AS, Kameoka Y, Kanda S, Niho Y, Suzuki K. Arginine to cysteine mutation (R499C) found in a Japanese patient with complete myeloperoxidase deficiency. Gene Expr. 2006. 13(2):67-71. [Medline].

  15. Nauseef WM. Diagnostic assays for myeloperoxidase and myeloperoxidase deficiency. Methods Mol Biol. 2014. 1124:537-46. [Medline].

  16. Nauseef WM. How human neutrophils kill and degrade microbes: an integrated view. Immunol Rev. 2007 Oct. 219:88-102. [Medline].

  17. Mauch L, Lun A, O'Gorman MRG, et al. Chronic granulomatous disease (CGD) and complete myeloperoxidase deficiency both yield strongly reduced dihydrorhodamine 123 test signals but can be easily discerned in routine testing for CGD. Clin Chem. Mar 2007. 53:890-896. [Medline].

  18. Boxer LA, Blackwood RA. Leukocyte disorders: quantitative and qualitative disorders of the neutrophil, part 2. Pediatr Rev. 1996 Feb. 17(2):47-50. [Medline].

  19. DeLeo FR, Goedken M, McCormick SJ, Nauseef WM. A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic reticulum/proteasome degradation. J Clin Invest. 1998 Jun 15. 101(12):2900-9. [Medline]. [Full Text].

  20. Marchetti C, Patriarca P, Solero GP, Baralle FE, Romano M. Genetic characterization of myeloperoxidase deficiency in Italy. Hum Mutat. 2004 May. 23(5):496-505. [Medline].

  21. Marchetti C, Patriarca P, Solero GP, Baralle FE, Romano M. Genetic studies on myeloperoxidase deficiency in Italy. Jpn J Infect Dis. 2004 Oct. 57(5):S10-2. [Medline].

  22. Milla C, Yang S, Cornfield DN, et al. Myeloperoxidase deficiency enhances inflammation after allogeneic marrow transplantation. Am J Physiol Lung Cell Mol Physiol. 2004 Oct. 287(4):L706-14. [Medline]. [Full Text].

  23. Molin L, Stendahl O. The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Acta Med Scand. 1979. 206(6):451-7. [Medline].

  24. Nauseef WM. Myeloperoxidase deficiency. Hematol Pathol. 1990. 4(4):165-78. [Medline].

  25. Nauseef WM. Myeloperoxidase deficiency. Hematol Oncol Clin North Am. 1988 Mar. 2(1):135-58. [Medline].

  26. Nauseef WM. Quality control in the endoplasmic reticulum: lessons from hereditary myeloperoxidase deficiency. J Lab Clin Med. 1999 Sep. 134(3):215-21. [Medline].

  27. Nauseef WM, Cogley M, Bock S, Petrides PE. Pattern of inheritance in hereditary myeloperoxidase deficiency associated with the R569W missense mutation. J Leukoc Biol. 1998 Feb. 63(2):264-9. [Medline].

  28. Petrides PE. Molecular genetics of peroxidase deficiency. J Mol Med. 1998 Sep. 76(10):688-98. [Medline].

  29. Petrides PE, Nauseef WM. Molecular and clinical aspects of neutrophil peroxidase deficiency: multidisciplinary approaches on an international scale. J Mol Med. 1998 Sep. 76(10):659-60. [Medline].

  30. Stendahl O, Molin L, Dahlgren C. The inhibition of polymorphonuclear leukocyte cytotoxicity by dapsone. A possible mechanism in the treatment of dermatitis herpetiformis. J Clin Invest. 1978 Jul. 62(1):214-20. [Medline]. [Full Text].

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