Methemoglobinemia

What is methemoglobinemia?

Methemoglobinemia (MetHb) is a very rare blood disorder, sometimes called “blue baby syndrome,” which affects how red blood cells deliver oxygen to cells and tissues. People can inherit this condition but MetHb usually happens when people use certain medications or recreational drugs or exposure to certain chemicals. MetHb can be life-threatening, especially for babies born with a severe type of the condition or people who use recreational drugs. Most of the time, healthcare providers treat methemoglobinemia with a medication that reduces methemoglobin levels and eliminates symptoms.

How does this affect my body?

Most people with methemoglobinemia have some level of cyanosis — a condition that turns your nail beds, tongue, lips and skin a distinctive shade of light blue or purple. Cyanosis happens when you don’t have enough oxygen in your blood. Normally, red blood cells carry oxygen throughout your body. Red blood cells rely on the protein hemoglobin to carry oxygen. In MetHb, a genetic mutation turns hemoglobin into methemoglobin. Methemoglobin doesn’t carry oxygen. Without adequate blood oxygenation — the amount of oxygen in your blood — you develop cyanosis.

What are methemoglobinemia symptoms?

Symptoms vary depending on the condition type. Most people with MetHb develop the condition because they use certain pain medications or recreational drugs or they were exposed to certain toxic substances. This is acquired methemoglobinemia and symptoms may include:

• Pale skin (pallor).
• Fatigue.
• Weakness.
• Headache.

Sometimes, people with acquired methemoglobinemia may have symptoms that require immediate medical attention. Those may include:

• Nausea and vomiting.
• Extreme drowsiness, slurred speech and slow reflexes: These are signs of central nervous system depression.
• Loss of consciousness or uncontrollable jerking motions: These are signs of seizures.
• Rapid breathing, increased heart rate and confusion: These are signs of metabolic acidosis.

Call 911 if you’re with someone who’s showing signs of seizure, metabolic acidosis or central nervous system depression.

What are congenital methemoglobinemia symptoms?

Congenital methemoglobinemia is very rare, with only a few cases documented worldwide. Based on what they’ve learned, healthcare providers have established three classifications of congenital methemoglobinemia — Type 1, Type 2 and hemoglobin M disease (HbM).

People with hemoglobin M disease often have cyanosis but are otherwise healthy. People with Type 1 MetHb have cyanosis but rarely have other medical issues. On the other hand, babies born with Type 2 MetHb often develop severe neurological issues by the time they’re 9 months old and rarely live beyond infancy.

What causes methemoglobinemia?

People inherit this condition or develop it after using certain medications, recreational drugs or being exposed to certain toxins. Less frequently, people inherit a form of this condition.

Acquired methemoglobinemia causes

The pain-killing medications benzocaine and lidocaine and the antibiotic dapsone can cause this condition. People also may develop methemoglobinemia after they’re exposed to nitrates used in some medications, nitrites (chemicals used in food preservatives and well water) and certain herbicides used in agriculture.

People who use recreational drugs like amyl nitrite (poppers), nitrous oxide (laughing gas) and local anesthetics or painkillers used to “cut” cocaine have an increased risk of life-threatening medical issues caused by very high methemoglobin levels.

Congenital (inherited) methemoglobinemia causes

Two different genetic mutations cause congenital MetHb. In Type 1 and Type 2, the CYB5R gene mutates, affecting the balance of hemoglobin and methemoglobin in your red blood cells. Hemoglobin M disease happens when several hemoglobin M genes mutate.

Congenital methemoglobinemia is an autosomal recessive disorder, meaning both parents have genetic mutations they pass on to their biological children. Hemoglobin M disease is autosomal dominant, meaning one parent passes a genetic mutation on to their biological children.

How do healthcare providers diagnose methemoglobinemia?

Healthcare providers diagnose this condition by taking complete medical histories and doing physical examinations. They may ask people with symptoms of acquired MetHb if they use certain recreational drugs or if they’ve been exposed to certain toxic substances.

What tests do healthcare providers use to diagnose this condition?

Healthcare providers typically do the following tests:

• Blood tests: People with this condition often have dark brown-colored arterial blood. The dark-brown color is a sign arterial blood isn’t carrying oxygen.
• MetHb evaluation: Healthcare providers measure methemoglobin levels in your blood.
• CYB5R enzyme activity: Lower-than-normal enzyme activity is a sign of congenital methemoglobinemia.
• Genotyping: Healthcare providers may do genotyping, examining your DNA for signs of genetic differences to confirm suspected congenital methemoglobinemia. Genotyping also helps healthcare providers identify the condition type.
• Hemoglobin electrophoresis: This is a technique healthcare providers use to examine hemoglobin in your red blood cells. They may use this test when diagnosing HbM.

How do healthcare providers treat this condition?

Treatment varies based on the kind of methemoglobinemia that you have. For example, a newborn with the Type 2 form of the condition will need very different treatment from someone who developed the condition because they were exposed to toxic substances or used certain recreational drugs.

People with Type 1 methemoglobinemia or Hemoglobin M disease may not need treatment. If they do, healthcare providers may use the following medications to reduce methemoglobin levels:

• Methylene blue: The medication is a well-known antidote for methemoglobinemia.
• Vitamins C and B2.

Treatment for acquired methemoglobinemia

Depending on circumstances, acquired methemoglobinemia may be a medical emergency that requires immediate treatment such as intravenous hydration and oxygen. Most people with acquired MetHb receive methylene blue.

What are treatment complications?

People with G6PD deficiency may develop hemolysis if they have repeated methylene blue treatments. Hemolysis happens when your red blood cells fall apart earlier than usual or inappropriately.

How can I reduce my risk of developing methemoglobinemia?

People who inherited a type of this condition should avoid toxic substances such as pesticides, some medications and most local anesthetics that may cause methemoglobin levels to rise. If you have this condition, ask a healthcare provider about substances and medications you should avoid.

People who use recreational drugs such as amyl nitrite or cocaine increase their risk of developing methemoglobinemia. If you use these drugs and you want help quitting, talk to a healthcare provider about potential treatments or programs that may help you.

What can I expect if I have this condition?

Most of the time, treatment eliminates symptoms. Most people with Type 1 congenital methemoglobinemia or Hemoglobin M disease have few symptoms and typically live as long as people who don’t have the condition.

How do I take care of myself?

In general, people born with a congenital form of the condition should be careful to avoid medications and substances that may trigger the condition. Everyone’s situation is a bit different, so it’s a good idea to ask your healthcare provider for guidance. People who have acquired MetHb should avoid the substances — recreational drugs, topical painkillers or toxic chemicals — that caused the condition.

When should I see my healthcare provider?

If you inherited a type of methemoglobinemia, you should contact your healthcare provider if you notice changes in your body such as fatigue or weakness. These symptoms may be signs your red blood cells are carrying even less oxygen throughout your body. People who have cyanosis and more serious symptoms, like seizures or extreme drowsiness, should call 911 or go to the emergency room.

What questions should I ask healthcare providers?

Methemoglobinemia is a very rare blood disorder that some people inherit (congenital MetHb) but most people develop (acquired MetHb). Depending on your situation, you may want to ask your healthcare provider some of the following questions:

Acquired MetHb

• Why do I have this condition?
• Will treatment make my symptoms go away?
• Will my symptoms come back?
• What should I do to prevent another incident?

Type 1 congenital MetHb

• Is cyanosis a serious medical issue?
• Will I always need treatment for MetHb?
• Will I develop other symptoms?
• Can I pass this condition on to my biological children?

Type 2 congenital MetHb

• How will this condition affect my baby?
• Are there treatments to ease my baby’s symptoms?
• What can I do to help my baby?
• If I have more children, will they have this condition?

A note from Cleveland Clinic

Methemoglobinemia (MetHb) is a rare blood disorder that affects how red blood cells deliver oxygen throughout your body. Some people inherit the disorder, but most people develop it after using certain medications, being exposed to certain toxic substances or using recreational drugs. Congenital methemoglobinemia rarely causes serious medical issues. (Sadly, some babies born with the condition have serious neurological issues.) People who develop the condition may develop life-threatening medical conditions. If you think you may be at risk of developing MetHb, talk to a healthcare provider about your situation. They’ll be glad to help.