Methemoglobinemia

Methemoglobinemia (MetHb) is a rare blood disorder. It affects how your red blood cells deliver oxygen throughout your body. Red blood cells need hemoglobin to carry oxygen. With MetHb, a chemical reaction or inherited genetic change turns hemoglobin into methemoglobin. This type of hemoglobin can’t release oxygen, so you develop cyanosis.

With cyanosis, your skin, lips or nail beds turn light blue or purple. They may look gray or light gray if you have darker skin tones. This symptom means your organs, muscles and tissues aren’t getting the amount of oxygen they need. Cyanosis is also the most common symptom of methemoglobinemia (pronounced “meh-the-moe-glob-in-me-ah”).

Types

There are two types of this condition:

• Acquired MetHb: Acquired means you develop it during your lifetime. Recreational drug use is the most common cause of acquired methemoglobinemia.
• Congenital MetHb: Congenital means it’s present at birth. Inherited genetic changes cause the congenital form. Severe forms of this disease can be life-threatening.

Symptoms of methemoglobinemia

The symptoms of the condition vary depending on type and methemoglobin levels. People with low levels may not have symptoms. But high levels can cause life-threatening complications.

Acquired MetHb symptoms

Acquired methemoglobinemia is the most common type. It may cause symptoms like:

• Skin, nail beds, lips and tongue that look light blue, purple, light gray or gray
• Pallor (very pale skin)
• Fatigue
• Weakness

People with high levels may have more serious symptoms, including:

• Nausea and vomiting
• Extreme drowsiness, slurred speech and slow reflexes if the disease affects their central nervous system
• Loss of consciousness or uncontrollable jerking motions that seizures may cause
• Rapid breathing, increased heart rate and confusion if the condition causes metabolic acidosis

If you’re with someone with these symptoms, call 911 or take them to an emergency room.

Congenital methemoglobinemia symptoms

The three subtypes of this condition are Type 1, Type 2 and hemoglobin M disease (HbM).

People with Type 1, or HbM, have cyanosis symptoms. But they won’t have other medical issues related to methemoglobinemia. With Type 2, babies have symptoms of cyanosis and may have serious neurological issues, including:

• Heads that are smaller than usual (microcephaly)
• Muscle movements they can’t control (dystonia)
• Seizures
• Growth faltering (failure to thrive)
• Intellectual disabilities

Neurological issues in Type 2 MetHb can be life-threatening. If your baby has this condition, their healthcare providers will explain how the condition affects your child and what they can do to help.

Methemoglobinemia causes

The acquired and congenital forms of this condition have different causes:

Acquired methemoglobinemia causes

This type happens when certain substances trigger a chemical reaction that turns hemoglobin into methemoglobin. Substances that may do this include:

• Recreational drugs: Volatile nitrites (poppers), nitrous oxide (laughing gas) or cocaine mixed with local anesthetics and can cause the reaction.
• Certain medications: The antibiotic dapsone and the pain medications benzocaine and lidocaine may cause it.
• Certain chemicals: Exposure to high levels of nitrites, nitrates and herbicides may cause the reaction. Nitrites and nitrates are chemicals in water and soil. People use them to preserve food. Farmers use herbicides to protect their crops.

Congenital methemoglobinemia causes

Two genetic variations cause the congenital type:

• Types 1 and 2: Changes in the CYB5R gene affect the balance of hemoglobin and methemoglobin in your red blood cells. In these types, both biological parents pass the genetic change on to their children.
• Hemoglobin M disease: This type happens when there’s a change in an alpha globin gene. The change affects hemoglobin so babies are born with high methemoglobin levels. In this type, one biological parent passes the genetic changes on to their children.

Complications of methemoglobinemia

High methemoglobin levels can be life-threatening, particularly if recreational drug use is the cause. It can be a fatal condition for babies with Type 2 congenital MetHb.

How doctors diagnose this condition

With acquired MetHb, healthcare providers will do a physical exam and ask about your medical history. They may ask if you take specific recreational drugs or spend time around herbicides, nitrites or nitrates. They may do blood tests, including:

• Arterial blood test: Providers will check your arterial blood. Dark brown arterial blood is a sign that it isn’t carrying oxygen.
• MetHb evaluation: This test measures methemoglobin levels.

Providers may do additional blood tests to diagnose congenital MetHb:

• CYB5R enzyme activity: Lower-than-normal enzyme activity is a sign of this condition type.
• Hemoglobin electrophoresis: The test lets healthcare providers check hemoglobin in your baby’s red blood cells. They may use it to diagnose hemoglobin M disease.
• Genetic tests: Providers may analyze your baby’s blood or saliva to diagnose the specific congenital type. They also check for genetic changes that caused the condition.

How is methemoglobinemia treated?

Treatment varies depending on the condition type and severity, but most people receive:

• Methylene blue: This medication lowers high methemoglobin levels, which helps your red blood cells carry and release oxygen throughout your body.
• Vitamins C and B2: These vitamins also reduce methemoglobin levels. They’re an alternative treatment for people with G6PD deficiency. Methylene blue may cause complications if you have G6PD deficiency.

Acquired methemoglobinemia may be a medical emergency that requires immediate treatment for seizures and central nervous system issues. Healthcare providers will treat the underlying condition. They’ll use methylene blue, intravenous hydration and oxygen as treatment.

Babies with Type 2 methemoglobinemia will need intensive and ongoing treatment for the serious issues the condition can cause.

Recovery time

Methylene blue often eases symptoms of cyanosis within hours. Recovery takes much longer for people with complications from severe MetHb.

When should I see my healthcare provider?

If you have MetHb, contact your healthcare provider if your symptoms continue after treatment. If your baby has it, contact their healthcare team if cyanosis or other symptoms don’t improve with treatment or get worse.

What’s the outlook for people with MetHb?

Most people with Type 1 congenital methemoglobinemia or Hemoglobin M disease typically live as long as people who don’t have the disease.

The outlook for people with Type 2 or severe acquired methemoglobinemia depends on their specific situation.