Methemoglobinemia (Congenital)

Congenital presence of high levels of methemoglobin in blood. Presence of abnormally high levels of methemoglobin in the blood because of a congenital anomaly of one chain of hemoglobin (hemoglobins M) or congenital deficit in NADH-cytochrome b5 reductase.

• Hemoglobins M
• Congenital Deficit in NADH-Cytochrome b5 Reductase

Mutations in cytochrome b5 reductase activity were identified in 1943 by Quentin Gibson, which was considered a “Tour de Force" of clinical investigation. Gibson subsequently went on to become one of the world's leading biochemists.

Rare. There are no epidemilogical studies on congenital methemoglobinemia.

Autosomal dominant (hemoglobins M) but a high rate of new mutations or recessive (congenital deficit in cytochrome b5 reductase) with a gene located on chromosome 22 q 13.31-qter.

Hemoglobins M: Five different mutations of hemoglobin (Hb) are known to produce congenital methemoglobinemia: Hb MBoston, Hb MIwate, Hb MSaskatoon, Hb MHyde Park, and Hb MMilwaukee. Congenital Deficit in NADH-Cytochrome b5 Reductase: Two types: type I in which the deficit is limited to the red blood cells, and type II in which the deficit is generalized (brain, liver, muscle, etc.). In red blood cells, the enzyme is present in its soluble form and is responsible for reversing the spontaneous oxidation of hemoglobin to methemoglobin. In other cells, it is located in the membrane of many organelles (Golgi system, microsomes, mitochondria) and is involved in the recycling of vitamin E and in the synthesis of cholesterol and cerebral lipids.

Measurement of dyshemoglobins with a co-oximeter. Hemoglobins M: Methemoglobinemia above 25% leads to cyanosis unaffected with oxygen administration, blood that is chocolate color, headache, confusion, chest pain, and weakness. Congenital Deficit in NADH-Cytochrome b5 Reductase: Measurement of enzymatic activity in red cells and fibroblasts

The patient's coloring is more grayish than truly cyanotic and the blood appears brown on inspection. Hemoglobins M: Cyanosis is present from birth if mutation is on the α chain, later if mutation is on the β chain of hemoglobin (when hemoglobin F is replaced by hemoglobin A). It is well tolerated and requires no treatment.

Congenital Deficit in Cytochrome b5 Reductase: Type I: Cyanosis from birth; it is very well tolerated and varies with temperature and exercise. Headache and palpitations when methemoglobinemia is greater than 50%. Patients are very sensitive to exogenous methemoglobin-producing agents.

Congenital reductase Type II: Cyanosis from birth but accompanied by irritability, vomiting, and feeding problems. By age 6 to 9 months, profound mental retardation is present, with microcephaly, nystagmus, athetosis, and attacks of hypertonia. Seizures are frequent, and death usually occurs before age 10 years as a consequence of pulmonary infections (chronic aspiration).

Determine the precise cause of methemoglobinemia.

Monitoring of hemoglobin oxygen saturation with pulse oximetry is unreliable. In case of worsening hemoglobinemia in a patient with type I congenital deficit of NADH-cytochrome b5 reductase, methylene blue 1 to 3 mg/kg should be administered intravenously (more than 5 mg/kg could induce hemolysis or methemoglobinemia by itself).

Methemoglobinizing agents such as benzocaine, prilocaine, quinine, metoclopramide, sulfamides, dapsone, and chloral hydrate should be avoided.

Rare cases of abnormal fetal hemoglobin M have been described. Cyanosis disappears in infancy when hemoglobin F is replaced by hemoglobin A.