Erythrocyte reductase deficiency

Definition

Methemoglobinemia is a blood disorder in which the body cannot recycle hemoglobin after it is damaged. 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.

Alternative Names

Causes

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 an autosomal recessive condition, which means it is passed on by both parents who usually do not have the condition themselves. It occurs when there is a problem with an enzyme called cytochrome b5 reductase. There are two subtypes of autosomal recessive 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. It is an autosomal dominant condition. That means only one parent needs to pass you the abnormal gene in order for you 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 spoilage of meat)

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

Symptoms

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

• Bluish coloring of the skin and mucous membranes

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 and mucous membranes
• Mild breakdown of red blood cells

Symptoms of acquired methemoglobinemia include:

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

Exams and Tests

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.

Treatment

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

Ascorbic acid may also be used to reduce the level of methemoglobin.

Alternative treatments include hyperbaric oxygen therapy and exchange transfusions.

In most cases of mild acquired methemoglobinemia, no treatment is required, other than avoiding the medicine or chemical that caused the problem. However, treatment (such as a transfusion) may be needed in severe cases.

Outlook (Prognosis)

Persons 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.

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

Possible Complications

• Shock
• Seizures
• Death

When to Contact a Medical Professional

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.

Prevention

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

Jaffe ER, Hultquist DE. Cytochrome b5 reductase deficiency and enzymopenic hereditary methemoglobinemia. In: Scriver CR, Beaudet AL, Sly WS, et al, eds. The Metabolic and Molecular Basis of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995:2267-2280.