Congenital Methemoglobinemia

Navajo Indians, Alaskan Indians, and people of Puerto Rican and Cuban ancestry

Normal life span (except for RCM type II)

Oxidizing agents may increase MetHb to dangerous levels.

Mild respiratory/cardiac depression may adversely affect pts with already limited reserve.

Pregnancies not compromised.

Measurement of SpO ₂

Oxidant drugs (e.g., prilocaine, benzocaine, nitroglycerin, sulfonamides, phenacetin, and nitric oxide), which are contraindicated

Myocardial ischemia due to decreased O ₂ delivery

Blood loss/anemia due to O ₂ -carrying capacity already reduced

Enzyme deficiency: Shift of O ₂ dissociation curve to the left leads to mild erythrocytosis (normal RBC life span).

RCM type I defect restricted to red cell soluble cytochrome b5 reductase only. Cyanosis is sole clinical symptom. Homozygotes have compensatory increase in RBC mass. Heterozygotes may develop acute symptomatic methemoglobinemia after exposure to exogenous MetHb-inducing agents. Defect may be the cause of unexplained periop cyanosis.

RCM type II: Defect occurs in all cells and involves both soluble and microsomal forms of cytochrome b5 reductase. Results include mental retardation, spasticity, opisthotonos, microcephaly, growth retardation, and death by 2–3 y of age.

RCM type III: Nonerythroid enzyme deficiency, but CNS spared.

HbM variations: Alpha chain variants affected from birth, and beta chain variants by 3–6 mo of age. Patients develop mild hemolytic anemia.

RCM types I, II, and III: Occur by autosomal recessive inheritance because of deficient reducing capacity of oxidized heme caused by NADH cytochrome b5 reductase (diaphorase) deficiency.

HbM variants: Occur by autosomal dominant inheritance due to structural abnormality in globin moiety; amino acid substitutions create abnormal environment for heme residues, displacing the equilibrium toward the ferric state.