|Values are valid only on day of printing.|
Confirming cases of suspected methemoglobin reductase (cytochrome b5 reductase) deficiency
Functional studies in families with methemoglobin reductase (cytochrome b5 reductase) deficiency
Methemoglobin reductase, also called "diaphorase," and more properly called cytochrome b5 reductase, is the enzyme within the erythrocyte that maintains hemoglobin in the reduced (non-methemoglobin) state.
Persons who are heterozygous for methemoglobin reductase mutations have no clinical or laboratory abnormalities, are not cyanotic, and have normal methemoglobin concentrations in their blood. However, they hold an increased risk for more severely symptomatic acute episodes of methemoglobinemia with exposure to inducing agents.
Persons who are homozygous for methemoglobin reductase mutations have normal arterial oxygen saturation but have varying quantities of methemoglobin in their blood, generally 15% to 20%, and are quite cyanotic. Paradoxically, homozygotes typically have normal blood counts; the condition only rarely causes polycythemia. The presence of methemoglobin shifts the hemoglobin-O2 dissociation curve to the right, so that although the transport of oxygen is diminished, the delivery of oxygen to tissues is normal. Because of the chronicity, the homozygous condition is usually compensated and therefore quite benign, but may cause concern to parents of affected children, be a cosmetic embarrassment to the children, and alarm the attending physician. The cyanosis may be treated with methylene blue.
> or =12 months: 6.6-13.3 U/g Hb
Reference values have not been established for patients who are <12 months of age.
Methemoglobin reductase (cytochrome b5 reductase) activity in neonates (0-6 weeks) is normally 60% of the normal adult value. Adult values are attained by 2 to 3 months of age.
Heterozygotes have results slightly lower than the reference range. Homozygotes demonstrate little to no methemoglobin reductase activity and increased levels of methemoglobin.
Individuals who are glucose-6-phosphate-dehydrogenase (G-6-PD) deficient are not candidates for methylene blue therapy. Administration of methylene blue to such persons will cause hemolysis or methemoglobin formation.
Beutler E: Methemoglobinemia and other causes of cyanosis. In Williams Hematology. Sixth edition. Edited by E Beutler, M Lichtman, WJ Williams, TJ Kipps. New York, McGraw-Hill Book Company, 2001, p 611