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.
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
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
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
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
Monitoring of hemoglobin oxygen ...