Methemoglobinemia is a condition in which the iron in the hemoglobin molecule (the red blood pigment) is defective, making it unable to carry oxygen effectively to the tissues.

Causes, incidence, and risk factors

There are two forms of inheritable methemoglobinemia, Type I and Type II.

Most hereditary cases are Type II, and result from a deficiency in the enzyme cytochrome b5 reductase. The other inheritable type, called hemoglobin M disease (Type I), is an autosomal dominant condition (you only need one affected parent to inherit it) characterized by an inability to convert methemoglobin back to Hemoglobin. This usually causes few problems.

Exposure to certain chemicals may also cause an increase in the production of methemoglobin. These chemicals include nitrites (used commonly to prevent spoilage of meat), xylocaine, and benzene.


  • In patients with type II congenital cytochrome b5 reductase deficiency: mental retardation, developmental delay, failure to thrive. They may also have seizures and other neurologic problems. Most die in infancy.  
  • In most patients with congenital methemoglobinemia (type I): a bluish discoloration to the skin and mucous membranes.  
  • In patients with acquired methemoglobinemia from chemical exposure: headache, fatigue, Shortness of breath, lack of energy, and potentially shock, seizures, and death.

Signs and tests

  • cyanosis (bluish skin color) with a normal level of oxygen in the blood (Pa02 on blood gas)  
  • abnormal optical spectrum of Hemoglobin  
  • incubation of blood with methylene blue is used to differentiate between cytochrome b5R deficiency and Hemoglobin M disease

Medications used to treat this disorder include:

  • methylene blue or 1 to 2 grams of ascorbic acid daily (to treat type I or II b5R deficiency)  
  • cyanosis caused by hemoglobin M disease tends to be benign but does not respond to treatment  
  • cyanosis caused by exposure to an offending chemical is treated by avoiding that chemical, blood or exchange transfusion for a patient in shock, and repeated doses of IV methylene blue


In acute exposure:

  • shock  
  • seizures  
  • death

Calling your health care provider

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

Call your health care provider or emergency services immediately if there is severe Shortness of breath.

Genetic counseling is recommended for prospective parents with a family history of methemoglobinemia.

Johns Hopkins patient information

Last revised: December 3, 2012
by Levon Ter-Markosyan, D.M.D.

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