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My name is Scott Reading.
I'm an Adjunct Assistant Professor in
the Department of Pathology in Division of Hematology at the University of Utah
and an investigator at
ARUP Laboratories Institute for Clinical and Experimental Pathology
in Salt Lake City Utah.
The topic of this presentation is
Cytochrome b5 Reductase Deficiency as it relates to Hereditary Methemoglobinemia.
I will be following this outline for the presentation.
I'll briefly review how Methemoglobin is formed and discuss
how it interferes with the proper transport of oxygen in the body.
I will then introduce different causes of Methemoglobinemia and discuss
in detail the role of Cytochrome b5 reductase in this disorder.
This discussion will illustrate two clinical phenotypes and outline what is known
about the various mutations and how they can
change the function of this important enzyme.
Next, I will discuss the differential diagnosis of Methemoglobinemia caused by
Cytochrome b5 reductase deficiency and contrast this with
other types of Methemoglobinemia caused by genetic or acquired conditions.
In closing, I will discuss suggested therapies for Methemoglobinemia.
To understand the origin of Methemoglobin,
we must start with Hemoglobin.
Hemoglobin is the principal component of red blood cells
responsible for carrying oxygen from the lungs to the tissues.
It is a tetrameric protein complex composed of four globin subunits.
At the center of each globin subunit is
a ferrous iron containing porphyryn ring co-factor called heme.
The ferrous iron binds molecular oxygen from the lungs
converting the ferro-deoxyhemoglobin to ferry-oxyhemoglobin.
Methaemoglobin is an altered state of Hemoglobin.
This occurs when the ferrous iron of
heme in deoxyhemoglobin is oxidized to the ferric state.
In the ferric state, the iron is no longer able to bind molecular oxygen.
In addition, as Hemoglobin is a tetrameric protein with four globin subunits,
when one of these globin subunit hemes is converted to the ferric state.
It affects the other ferrous hemes to have a greater affinity for oxygen.
That result is a decreased ability of
that Hemoglobin molecule to deliver oxygen to the tissues.