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A large proportion of hemoglobin in young infants is in the form of fetal hemoglobin. Fetal hemoglobin is more readily oxidized to methemoglobin by nitrites than is adult hemoglobin. Also, in infants, NADH-dependent methemoglobin reductase, the enzyme responsible for reduction of induced methemoglobin back to normal hemoglobin, has only about half the activity present in adults.

  1. Hemolytic anemia or sulfhemoglobinemia can be caused by many substances that induce methemoglobinemia.

  2. The level of methemoglobinemia can be measured with a Co-Oximeter. Although biologic nitrate and nitrite levels can be determined, these tests are not routinely performed; it is more expedient to identify and measure nitrate at its source (e.g., contaminated well water). If congenital methemoglobinemia is suspected or if the patient responds poorly to treatment with methylene blue, the following tests should be performed: hemoglobin electrophoresis, G-6-PD activity, and the activities of NADH- and NADPH-dependent methemoglobin reductases.

  3. Some patients may not respond to methylene blue treatment because they have a G-6-PD deficiency, sulfhemoglobinemia, or hemoglobin M disease.

  4. Treatment options for patients with G-6-PD deficiency include exchange transfusion and hyperbaric oxygen therapy.

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