What Is Methemoglobinemia?

Methemoglobinemia is an uncommon medical condition that makes some of the red blood cells unable to transport oxygen. Symptoms can range from absent to mild to life-threatening.

Usually, methemoglobinemia results from certain toxins or overexposure to certain drugs, like some anesthetics (drugs used to reduce pain and sensation). A smaller number of people also have methemoglobinemia due to genetic problems present from birth. 

This article will discuss some of the causes and symptoms of methemoglobinemia, as well as its diagnosis, treatment, and related issues.

Methemoglobinemia Causes

Your red blood cells contain an important protein called hemoglobin. In its normal state, this protein transports life-giving oxygen to all the cells of your body. Specifically, iron in the hemoglobin picks up oxygen that is taken around the body. Hemoglobin also gives blood its reddish color. 

Methemoglobin is a form of hemoglobin that is a little different from normal hemoglobin. Because of a slight difference in the form of iron it contains, it can’t pick up oxygen normally, so it can’t take it to parts of the body that need it. 

Methemoglobin is usually present at low levels in the body (less than 1% of total hemoglobin). However, when this percentage increases, it can cause problems. In methemoglobinemia, at least 3% or more of a person’s hemoglobin is in the form of abnormal methemoglobin.

Methemoglobinemia Symptoms

If you have only a little more methemoglobin in your blood than normal, you might not notice any symptoms. 

Because the body does a good job of compensating, people with mild, chronic methemoglobinemia might only learn of it when undergoing medical tests for other reasons. Sometimes methemoglobinemia only becomes apparent when a person is experiencing other problems, like recovering from surgery in the intensive care unit (ICU).

In contrast, if you have a higher percentage of methemoglobin, you could have life-threatening issues. 

Some possible symptoms are:

• Blue color to the skin and lips (cyanosis)
• Weakness
• Dizziness
• Nausea
• Shortness of breath
• Brownish blood

With severe methemoglobinemia, symptoms might include:

• Heart rhythm problems
• Impaired thinking
• Seizures
• Coma

Death is also possible in severe situations. 

Inherited Forms of Methemoglobinemia

Inherited methemoglobinemia (also called autosomal recessive methemoglobinemia or congenital methemoglobinemia) is caused by rare genetic problems present from birth. Different genetic problems lead to different levels of severity, which sometimes need slightly different treatments. There are two forms of inherited methemoglobinemia: types 1 and 2.

People with type 1 congenital methemoglobinemia often have an average lifespan and don't experience complications.

The affected gene in type 2 inherited methemoglobinemia leads to a problem with a protein (called cytochrome 5 reductase). This protein helps keep the iron in the right configuration for regular hemoglobin (and not methemoglobin). 

People with type 2 congenital methemoglobinemia have a severe problem with this protein. Because of this, symptoms are most severe for people with type 2 congenital methemoglobinemia. Most people with type 2 die in infancy. They also tend to have developmental delays and other neurological issues.

Other congenital disorders can also cause increased levels of methemoglobin. These include:

• Hemoglobin M disease
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Acquired Methemoglobinemia

Exposure to certain drugs or toxins can also trigger methemoglobinemia in some people. Some examples are:

• Anesthetics such as Xylocaine (lidocaine)
• Antibiotics like Aczone (dapsone) 
• Antimalarials like chloroquine
• Nitrites, such as from contaminated well water
• Pesticides, including exposure in farmers

However, not everyone exposed to these substances develops methemoglobinemia. Some people have a greater tendency toward developing it than others.

Diagnosis

A person’s symptoms, medical history, and physical exam results all provide important clues to consider methemoglobinemia. Certain medical tests also give key information. Some of these might be:

• Arterial blood gas: A test that measures the acidity (pH) and carbon dioxide and oxygen levels in the blood from an artery
• Co-oximetry: Analyzes blood gases, including hemoglobin and dyshemoglobins (hemoglobin that can't transport oxygen such as methemoglobin)
• Pulse oximetry: An electric device that measures oxygen saturation in your red blood cells

These all give information about the oxygenation status within your blood. The latter is less accurate, but unlike the others, you don't have to directly access a person's blood. Pulse oximetry screening can also sometimes help identify infants born with methemoglobinemia.

Other tests may also be necessary to rule out other more common causes of a person’s symptoms related to low oxygen (hypoxia).

Unlike most other people showing symptoms from poor levels of oxygen, people with methemoglobinemia don’t improve when given pure oxygen to breathe. This can be a clue that methemoglobinemia might be the problem.

Because methemoglobinemia is relatively rare but often reversible, it’s especially important that healthcare providers consider it as a possibility. 

Treatment

Treatment can vary based on the severity of methemoglobinemia, whether it is a sudden or chronic issue, and whether it is from exposure or a genetic cause. Severe methemoglobinemia requires immediate emergency treatment, but someone who has chronic mild methemoglobinemia may not need any treatment at all.

Some potential treatments include:

• Removal of the triggering substance 
• Infusion of methylene blue (promotes the conversion of methemoglobin to normal hemoglobin)
• Vitamin C (ascorbic acid)
• Vitamin B2 (riboflavin)
• Hyperbaric oxygen therapy (breathing pure oxygen in a pressurized environment)
• Red blood cell transfusion (in severe cases)

Prevention

People who have inherited forms of methemoglobinemia should avoid drugs known to trigger methemoglobinemia in some people. Information regarding this should be available on the drug's labeling information. Even if you’ve never had symptoms from it yourself, this information may be important if someone in your family has ever had such a problem. 

When starting new medications or considering surgery, discuss this complete medical history with your healthcare provider. You might need a different medication, or your surgical team may need to take additional precautions.

Summary

Methemoglobinemia is a medical condition in which much of your hemoglobin can’t transport oxygen normally because it is in the form of methemoglobin. It can be present from birth or triggered by something later in life. Symptoms might be absent, mild, or life-threatening, depending on severity. While severe methemoglobinemia requires immediate emergency treatment, those with mild methemoglobinemia may not need any treatment.

A Word From Verywell

It can be frightening to learn that you or a loved one has methemoglobinemia. The good news is that we have excellent treatments for acquired methemoglobinemia, even though its initial symptoms might be serious. Also, most people with inherited disease have a subtype with manageable symptoms and an average life span.