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Myeloperoxidase (MPO) deficiency

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Related Terms
  • Acquired myeloperoxidase deficiency, antifungals, antimicrobials, azurophilic granules, bacteria, cancer, cancerous, cancerous tumors, diabetes, diabetes mellitus, enzymatic, enzyme, fungal infection, fungi, fungus, gene, genetic disorder, genetic mutation, hereditary, heterozygotes, immune, immune defense system, immune system, immunology, infection, inherited myeloperoxidase deficiency, lysosomes, malignancy, malignant, microbe, microbial killing, monocytes, MPO, mutated gene, myeloperoxidase, neutrophils, peroxidase, phagocytosis, PMNs, polymorphonuclear leukocytes, tumor, white blood cells.

Background
  • Myeloperoxidase (MPO) is an iron-containing human enzyme that helps neutrophils and monocytes (types of white blood cells) destroy foreign substances like bacteria, fungi, and viruses that enter the body.
  • Myeloperoxidase deficiency, a disorder that occurs when individuals have abnormally low or nonexistent levels of the enzyme, was first described in 1954. Some patients who have MPO deficiency are unable to destroy substances that enter the body as efficiently as individuals who have the enzyme. However, most patients are asymptomatic (experience no symptoms) and the condition is usually undiagnosed.
  • In most cases the condition is inherited. When the condition is caused by other medical conditions, such as anemia, thrombotic diseases, or diabetes mellitus, it is called acquired MPO deficiency. Most acquired cases are temporary and resolve once the underlying cause is treated.
  • In general, most individuals with partial or complete MPO deficiency have no increased frequency of infections. This is because MPO-deficient neutrophils are able to phagocytose (engulf) most microbes normally.
  • However, the neutrophils' ability to actually kill the bacteria typically occurs at a slower rate. For instance, when bacteria like Staphylococcus aureus or Escherichia coli enter the body, it takes the neutrophils longer than normal to kill the bacteria. This indicates that the MPO-deficient cells use a different and slower method of killing the microbes.
  • The MPO-deficient neutrophils are completely unable to kill certain fungi and in vitro (test tube) studies have shown that Candida albicans, Candida krusei, Candida stellatoidea, and Candida tropicalis cannot be killed by MPO-deficient neutrophils.
  • Severe infections occur in fewer than five percent of patients with MPO deficiency. In general, infections only occur in patients who also have diabetes mellitus. The reason for this remains unknown.
  • Since most cases are undiagnosed, researchers initially thought that the condition was very rare. Only 15 cases reported worldwide before 1970. Today, technological advances in sciences have led researchers to believe the condition is more prevalent, with incidence rates from studies ranging from one case per 1,400 to 2,000 people in the United States.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
  1. DeLeo FR, Goedken M, McCormick SJ, et al. A novel form of hereditary myeloperoxidase deficiency linked to endoplasmic reticulum/proteasome degradation. J Clin Invest. 1998 Jun 15;101(12):2900-9. .
  2. Lanza F. Clinical manifestation of myeloperoxidase deficiency. J Mol Med. 1998 Sep;76(10):676-81. .
  3. Marchetti C, Patriarca P, Solero GP, et al. Genetic studies on myeloperoxidase deficiency in Italy. Jpn J Infect Dis. 2004 Oct;57(5):S10-2. .
  4. Natural Standard: The Authority on Integrative Medicine. . Copyright © 2007. Accessed April 6, 2007.

Causes
  • Inherited: Most cases of myeloperoxidase (MPO) deficiency are genetically inherited (passed down from parents to their children). Researchers believe that most MPO deficient patients are compound heterozygotes, which means that they have a different mutation (abnormality) on each copy of the gene (one from each parent)
  • As with many other genetic diseases, several different genetic combinations can lead to MPO deficiency. While several different genes have been shown to cause the disorder, researchers believe that many others have yet to be discovered.
  • The most common gene mutation that causes MPO deficiency is the R569W gene. Individuals with this mutated gene do not have any MPO in their neutrophils.
  • Another, less common genetic mutation that causes the disorder occurs when the Y173C gene is not formed properly. Individuals who have the mutated gene have MPO, but it is unable to fully mature.
  • A third genetic mutation that causes MPO deficiency occurs when the M251T gene does not form properly. Individuals with this mutated gene have fully mature MPO in their cells. However, the MPO is not functional, which means it is unable to destroy microbes that enter the body.
  • Another genetic mutation that causes MPO deficiency occurs when the G501S gene is not formed properly. However, researchers have not determined how this mutation causes the disorder.
  • Acquired: Acquired MPO deficiency is less common than the hereditary form. This condition is often temporary and it usually only causes a partial deficiency. Conditions that may lead to MPO deficiency include: pregnancy, lead intoxication (prevents heme synthesis, a component of mature MPO), iron deficiency, severe infection, thrombotic diseases, kidney transplantation, diabetes mellitus, neuronal lipofuscinosis (neurodegenerative disorder), drugs (cytotoxic agents and some anti-inflammatory agents like dapsone, 5-aminosalicylic acid, and sulfapyridine), cancers that have spread to multiple areas of the body (acute myeloid leukemia, chronic myeloid leukemia or Hodgkin's disease), refractory megaloblastic anemia, aplastic anemia, myelofibrosis with myeloid metaplasia, and myelodysplastic syndromes. The enzyme deficiency is corrected when the underlying condition is resolved.

Symptoms
  • Most patients who have myeloperoxidase (MPO) deficiency are asymptomatic (experience no symptoms).
  • There appears to be a strong association between total MPO deficiency and malignancies (cancerous tumors), according to studies. Researchers suspect that this is because MPO-deficient polymorphonuclear leukocytes are unable to stop tumor cells from growing.
  • In general, most patients with MPO deficiency do not experience an increased frequency of infections. Severe infections are uncommon, occurring in fewer than five percent of patients. If an infectious disease occurs, is it usually a fungal infection (like Candida albicans or Candida tropicalis) that occurs in a patient who also has diabetes mellitus. Patients with MPO deficiency who do not have diabetes rarely experience problems. However, the reason for this remains unknown.

Diagnosis
  • General: Since most patients who have myeloperoxidase (MPO) deficiency are asymptomatic (experience no symptoms), most cases are undiagnosed.
  • Blood smear: A blood smear is the standard diagnostic tool for MPO deficiency. During the procedure, a small sample of blood is taken from the patient and smeared onto a slide. The blood smear is then stained for peroxidase and observed under a microscope to determine whether MPO is present in the neutrophils. If MPO is not present, or if it is lower than normal, the patient is diagnosed with MPO deficiency.

Treatment
  • General: Most patients with myeloperoxidase (MPO) deficiency are asymptomatic (experience no symptoms) and require no treatment. Acquired MPO deficiency will resolve once the underlying condition is treated. In general, routine treatment with preventative antibiotics is not recommended because most patients with MPO deficiency do not have an increased incidence of infections.
  • Individuals with diabetes are the most likely to experience infections, particularly fungal infections. These infections are typically treated with antifungals. If the patient develops malignancies (cancerous tumors), cancer treatment, such as chemotherapy or radiation therapy, may be administered.
  • Antimicrobials: Patients who have MPO deficiency and diabetes are the most likely to develop infections, especially fungal infections. If infection occurs, antimicrobials are prescribed. Antibiotics are used to treat bacterial infections, antivirals are used to treat viral infections, and antifungals are used to treat fungal infections. Treatment regimens, including dosing and duration, depend on the severity and type of infection. Commonly prescribed antifungals include fluconazole (Diflucan®), amphotericin B (Fungizone®, AmBisome®, Abelcet®), fluconazole (Diflucan®), ketoconazole (Nizoral®), and voriconazole (Vfend®).

Integrative therapies
  • Good scientific evidence:
  • Zinc: Evidence from two human trials suggests that zinc pyrithione shampoo may be an effective treatment for tinea versicolor fungal infections of the scalp. No side effects were noted. Additional research is needed before a strong recommendation can be made. Zinc is regarded as a relatively safe and generally well-tolerated therapy, when taken at recommended doses, and few studies report side effects.
  • The recommended daily dose for adult and teenage males is 15 milligrams. The recommended daily dose for adult and teenage females is 12 milligrams. The recommended daily dose for pregnant females is 15 milligrams and the recommended daily dose for breastfeeding females is 16-19 milligrams. The recommended daily dose for children ages four to 10 is 10 milligrams and 5-10 milligrams for children zero to three years old. Zinc acetate should only be used during pregnancy or breastfeeding if clearly needed.
  • Unclear or conflicting scientific evidence:
  • Bitter orange: One controlled clinical trial found promising results using the oil of bitter orange as an antifungal agent. However, due to methodological weakness of the trial, further evidence is needed to confirm these results.
  • Avoid if allergic or hypersensitive to bitter orange or any members of the Rutaceae family. Avoid with heart disease, narrow-angel glaucoma, intestinal colic, and long QT interval syndrome. Avoid if taking anti-adrenergic agents, beta-blockers, QT-interval prolonging drugs, monoamine oxidase inhibitors (MAOIs), stimulants, or honey. Use cautiously with headache, hyperthyroidism (overactive thyroid), or if fair-skinned. Avoid if pregnant or breastfeeding.
  • Cranberry: Limited laboratory research has examined the antifungal activity of cranberry. There are no reliable human studies supporting the use of cranberry in this area.
  • Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium genus. Sweetened cranberry juice can affect blood sugar levels. Use cautiously with a history of kidney stones. Pregnant and breastfeeding women should avoid cranberry in higher amounts than what is typically found in foods.
  • Pomegranate: The extract of pomegranate was shown to be as effective as a commonly used oral gel when used topically to treat candidiasis (oral thrush) associated with denture stomatitis (mouth sores) in a randomized controlled trial. Pomegranate extract in combination with Centella asiatica extract was found to have a statistically significant benefit in periodontal plaque reduction compared to placebo.
  • Avoid if allergic or hypersensitive to pomegranate. Avoid with diarrhea or high or low blood pressure. Avoid taking pomegranate fruit husk with oil or fats to treat parasites. Pomegranate root/stem bark should only be used under the supervision of a qualified healthcare professional. Use cautiously with liver damage or disease. Pomegranate supplementation can be unsafe during pregnancy when taken by mouth. The bark, root, and fruit rind can cause menstruation or uterine contractions. Avoid if breastfeeding due to a lack of scientific data.
  • Propolis: The Brazilian commercial ethanol propolis extract, also formulated to ensure physical and chemical stability, was found to inhibit oral candidiasis in 12 denture-bearing patients with prosthesis stomatitis candidiasis association.
  • Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, or Balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.
  • Seaweed, kelp, bladderwrack: Laboratory research suggests antifungal and antibacterial activity of bladderwrack, which is a type of seaweed called kelp. However, there are no reliable human studies to support use as an antibacterial or antifungal agent.
  • Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.
  • Selenium: Commercially available 1% selenium sulfide shampoo has been reported as an equivalent to sporicidal therapy in the adjunctive treatment of tinea capitis infection, although further high-quality evidence is needed. Also, preliminary studies using the topical selenium (selenium sulfide shampoo) for tinea versicolor infections are inconclusive.
  • Avoid if allergic or sensitive to products containing selenium. Avoid with history of nonmelanoma skin cancer. Selenium is generally regarded as safe for pregnant or breastfeeding women. However, animal research reports that large doses of selenium may lead to birth defects.
  • Tea tree oil: Although tea tree oil is thought to have activity against several fungus species, there is insufficient information to drawn firm conclusions on the effectiveness of topical tea tree oil for onychomycosis (finger nail infections).
  • In laboratory studies, tea tree oil can kill fungus and yeast, such as Candida albicans. However, at this time there is not enough information available from studies in humans to make a firm conclusion. Tea tree oil can be toxic when taken by mouth and therefore should not be swallowed.
  • In laboratory studies, tea tree oil can kill yeast and certain bacteria. However, at this time, there is not enough information available from studies in humans to determine whether tea tree oil can effectively treat vaginal infections. Although tea tree oil may reduce itching caused by yeast or bacteria, it may also cause itching from dry skin or allergy.
  • Preliminary studies report tea tree oil to have activity against several fungal infections, including athlete's foot. Further research is needed before a firm conclusion can be made.
  • Avoid use if allergic to tea tree oil or plants of the Myrtle (Myrtaceae) family, Balsam of Peru, or banzoin. Use cautiously with history of eczema. Avoid taking tea tree oil by mouth because reports of toxicity have been documented. Avoid if pregnant or breastfeeding.

Prevention
  • Currently, there is no known method of prevention for myeloperoxidase (MPO) deficiency.
  • In general, routine treatment with preventative antibiotics is not recommended because most patients with MPO deficiency do not have an increased incidence of infections.

Copyright © 2011 Natural Standard (www.naturalstandard.com)


The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

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