What is Myeloperoxidase Deficiency?
Myeloperoxidase (MPO) is a protein present in certain types of white blood cells known as neutrophils and in the small enzyme-filled sacks of monocytes, another kind of white blood cell. This protein plays a crucial role in stopping bacterial infections because it can create powerful bacteria-killing substances like hypochlorous acid from hydrogen peroxide and chloride, a type of salt.[1][2][3]
Myeloperoxidase deficiency, first identified in 1954, is a genetic disorder caused by changes in the MPO gene located on the 17th chromosome. This disorder is passed down through families and is the most common genetic disorder affecting white blood cells known as phagocytes, which ‘eat’ and kill harmful microorganisms. People with MPO deficiency have weakened defenses against bacterial infections, but most do not show symptoms unless they also have diabetes. In this piece, we’ll delve more into this common disorder of the immune system.[4][5]
What Causes Myeloperoxidase Deficiency?
MPO stands for Myeloperoxidase and is a specific protein that is created from instructions provided by the MPO gene. This gene is located on a region of chromosome 17. The MPO consists of several parts and it plays a vital role in our immune system. Its primary job is to help white blood cells eliminate bacteria and other harmful substances in the body. It does this by producing a potent compound called hypochlorous acid (HOCl) and other harmful oxidants that attack and destroy invaders such as bacteria. They can also cause damage to certain parts of our body during an inflammation process.
MPO deficiency happens in two primary ways – inherited (primary) and acquired (secondary). In the inherited form, the deficiency is passed on from parents to children through their genes. This deficiency has different levels of severity and shows up in different ways for each individual. The MPO gene may have different mutations – changes in the genetic code – that lead to this deficiency. These mutations could appear at different stages of the MPO production process. Some of the common mutations include R569W, Y173C, M251T, G501S, R499C and a 14 bases deletion (D14) within a part of the MPO gene called exon 9. It’s important to note that a certain type of white blood cell called eosinophils are not affected by MPO deficiency as they are controlled by a different gene.
The secondary deficiency is less common but occurs due to changes in the MPO gene that happen after birth. This type of deficiency is usually only found in a portion of the white blood cells (neutrophils) and is often temporary. It usually improves once the underlying cause that led to the genetic change gets better.
Many conditions might lead to secondary MPO deficiency: diabetes, pregnancy, iron deficiency, kidney transplant, blood clot-related issues, lead poisoning, jaundice, spread cancers, blood disorders, tumours such as acute and chronic myeloid leukemia, myelodysplastic syndrome, polycythemia vera, Hodgkin lymphoma, serious infections, certain drugs that fight off cancer cells, and certain anti-inflammatory medicines like sulfapyridine.
Risk Factors and Frequency for Myeloperoxidase Deficiency
Myeloperoxidase (MPO) deficiency was once thought to be extremely rare, with only 17 known cases reported up until 1979. It was estimated to affect about 1 in 2,000 to 4,000 people in the United States and Europe, and 1 in 55,000 people in Japan. However, thanks to improved diagnostic methods, we now know that this disorder is more common than initially thought.
Signs and Symptoms of Myeloperoxidase Deficiency
Patients with MPO (Myeloperoxidase) deficiency do not typically show symptoms or have a higher rate of infections. However, there have been cases where patients with this condition, who also have other health issues like diabetes, suffer from frequent severe infections caused by Candida Albicans, a type of yeast. In these cases, it’s difficult to tell if the infections are due directly to the MPO deficiency or if there are other factors at play.
A research study in Europe found that only half of the patients with complete MPO deficiency had complications due to infections, while the other half had no symptoms at all. Only 10% of these patients had life-threatening complications due to infections.
The lack of serious infections in MPO deficient patients, as compared to patients with Chronic Granulomatous Disease (CGD), highlights the effectiveness of certain reactive oxygen species, like amplified hydrogen peroxide. These act as strong agents that kill bacteria and protect MPO deficient patients. However, the absence of MPO-mediated species such as Hypochlorous Acid (HOCl) seems to be a primary reason for the inability to stop fungal infections like Candidiasis from developing.
Testing for Myeloperoxidase Deficiency
When doctors suspect a medical condition called MPO deficiency, the first step they take in making a diagnosis is to test for peroxidase activity. Peroxidase is an enzyme involved in many important processes in your body. To test its activity, doctors use methods like staining white blood cells, immunocytochemistry, or something more commonly known as flow cytometry, which can check how well MPO (a type of peroxidase) is working inside a certain type of white blood cell called neutrophils. Testing for the presence of MPO protein in isolated white blood cells also gives them helpful information about the cause of any malfunctioning enzyme they may find.
Diagnosing MPO deficiency can be tricky because many other disorders show similar signs and symptoms. These include Chediak-Higashi syndrome, a condition with effects on the immune system and pigmentation; Hyperimmunoglobulinemia E, a rare immune disorder; leukocyte adhesion deficiency, a condition affecting the body’s ability to fight infections; neutropenia, a condition characterized by a low number of neutrophils; neutrophil actin dysfunction, a problem affecting the inner workings of cells; and lazy leukocyte syndrome, another rare immune disorder. There are also certain conditions that can cause a secondary MPO deficiency. So, if a patient has widespread fungal infections, MPO deficiency should be considered as a possible cause.
Treatment Options for Myeloperoxidase Deficiency
If you have MPO deficiency, a rare disorder affecting your immune system, you most likely will not show any symptoms and usually won’t be sick from infections. Because of this, physicians generally do not recommend preventative antibiotics. Nonetheless, if you also have diabetes, which can increase the risk of local and more widespread infections, doctors may advise swift and robust treatment with antibiotics to manage these infections.
It’s also wise to avoid treatments that could increase your chances of getting fungal infections. This includes long-term use of antibiotics or medications like steroids. These can upset the natural balance of microorganisms in your body and lead to an overgrowth of fungus.
What else can Myeloperoxidase Deficiency be?
Here’s a list of various medical conditions and syndromes:
- Chediak-Higashi syndrome
- Genetics of von Gierke disease
- Hyperimmunogloblinemia E syndrome
- Kostmann disease
- Lazy leukocyte syndrome
- Leukocyte adhesion deficiency
- Myelokathesis
- Neutropenia
- Neutrophil active dysfunction
- Pediatric chronic granulomatous disease
- Shwachman-Diamond syndrome
- Specific granule deficiency
