Methemoglobinemia is a blood disorder in which an abnormal amount of hemoglobin builds up in the blood. Hemoglobin is the oxygen-carrying molecule found in red blood cells. In some cases of methemoglobinemia, the hemoglobin is unable to carry oxygen effectively to body tissues.

Hemoglobin M disease; Erythrocyte reductase deficiency; Generalized reductase deficiency

Methemoglobinemia may be passed down through families (inherited). Or, it may result from exposure to certain drugs, chemicals, or foods (acquired).

There are two forms of inherited methemoglobinemia. The first form is passed on by both parents. The parents usually do not have the condition themselves, but they carry the gene that causes the condition. It occurs when there is a problem with an enzyme called cytochrome b5 reductase.

There are two types of this form of methemoglobinemia:

• Type 1 (also called erythrocyte reductase deficiency) occurs when red blood cells lack the enzyme.
• Type 2 (also called generalized reductase deficiency) occurs when the enzyme doesn't work anywhere in the body.

The second form of inherited methemoglobinemia, called hemoglobin M disease, is caused by defects in the hemoglobin molecule itself. Only one parent needs to pass on the abnormal gene in order for the child to inherit the disease.

Acquired methemoglobinemia is more common than the inherited forms. It occurs after exposure to certain chemicals and drugs, including:

• Anesthetics such as benzocaine and Xylocaine
• Benzene
• Certain antibiotics (including dapsone and chloroquine)
• Nitrites (used as additives to prevent meat from spoiling)

The condition may also occur in infants who are very ill or who are fed too many vegetables containing nitrates (such as beets).

Symptoms of type 1 methemoglobinemia (erythrocyte reductase deficiency) include:

• Bluish coloring of the skin

Symptoms of type 2 methemoglobinemia (generalized reductase deficiency) include:

• Developmental delay
• Failure to thrive
• Mental retardation
• Seizures

Symptoms of hemoglobin M disease include:

• Bluish coloring of the skin

Symptoms of acquired methemoglobinemia include:

• Bluish coloring of the skin
• Headache
• Fatigue
• Shortness of breath
• Lack of energy

Methemoglobinemia can be diagnosed with a blood test.

A baby with this condition will have bluish skin color (cyanosis) at birth or shortly thereafter. Arterial blood gases and pulse oximetry results will be normal, making the condition challenging to diagnose.

A medicine called methylene blue is used to treat persons with severe methemoglobinemia. Note: Methylene blue may be dangerous in patients who have or may be at risk for a blood disease called G6PD deficiency, and should not be used. If you or your child has G6PD deficiency, always tell your health care provider before receiving treatment.

Ascorbic acidmay also be used to reduce the level of methemoglobin.

Alternative treatments include hyperbaric oxygen therapyand exchange transfusions.

In most cases of mild acquired methemoglobinemia, no treatment is required. However, you should avoid the medicine or chemical that caused the problem. Severe cases may need treatment, such as a blood transfusion.

People with Type 1 methemoglobinemia and hemoglobin M disease usually do well. Type 2 methemoglobinemia is much more serious, and usually causes death within the first few years of life.

People with acquired methemoglobinemia usually do very well once the drug, food, or chemical that caused the problem is identified and avoided.

• Shock
• Seizures
• Death

Call your health care provider if you have a family history of methemoglobinemia and you develop symptoms of this disorder.

Call your health care provider or emergency services immediately if you have severe shortness of breath.

Genetic counseling is recommended for couples with a family history of methemoglobinemia who are considering having children.

DeBaun MR, Vichinsky E. Hemoglobinopathies. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th Ed. Philadelphia, PA: Saunders Elsevier; 2007: chap 462.

Gregg XT, Prchal JT. Red blood cell enzymopathies. In: Hoffman R, Benz EJ Jr., Shattil SS, eds. Hematology: Basic Principles and Practice. 5th ed. Philadelphia, PA: Elsevier Churchill Livingston; 2008: chap 45.