Metabolic
RBC Disorders
Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD deficiency)Anemia
can be caused by defects
in the metabolism that maintains the integrity of the red blood cell membrane.
An important enzyme deficiency is the G6PD deficiency, which is an X-linked
disorder and fully expressed in the male and in homozygous females. In heterozygous
females it is expressed in a variable fashion. There are more than 100 known mutants
of this disorder, but clinically the most important one is a drug sensitive variety
that affects approximately 10% of black males in the US and less than 10% female
blacks. People of Mediterranean origin are much less affected by this disorder.
Because the older red blood cells are affected in this disorder more than
the young ones, there is hemolysis of older RBC’s. Certain conditions that strain
RBC’s as well like fever, viral or bacterial infections and diabetic acidosis,
will lead to even more anemia by hemolysis. Certain drugs and substances can produce
peroxide and cause oxidation of hemoglobin and red blood cells, which in turn
can cause hemolysis. Simple drugs like ASA, sulfonamides, phenacetin, dapsone,
vitamin K derivatives, and even consuming fava beans will cause hemolysis in susceptible
people. There are enormous differences between people in the sense that the G6PD
deficiency is expressed in different degrees of severity (dependent on gene expression).
In blacks the older cell population of RBC’s is selectively targeted by hemolysis
putting a limit of less than 25% of the total RBC mass that can be affected. In
whites all of the RBC’s can be affected so that they tend to get a much more
severe hemolysis, which can be lethal in severe cases. The degree of severity
depends on the dose of the offending drug or substance and on how much peroxide
is formed by this toxic process. With severe hemolysis hemoglobinuria and kidney
failure can develop from the hemolytic process. Symptoms
A patient, who is anemic and has an acute hemolytic anemia with jaundice,
particularly in a black male, should be checked for G6PD deficiency. Chills, a
fever and pain in the back and in the stomach may accompany the anemia. Diagnosis
The reticulocytes are increased markedly during hemolysis. Heinz bodies
occur early in the illness, but are subsequently removed by the spleen. Also cells
that look like a bite was taken from the periphery (bit cells) are characteristic
of G6PD deficiency. Specific enzymes assays are available to come to the accurate
diagnosis. Treatment Treatment during a hemolysis
attack is supportive. It would be rare to require a transfusion of blood. Any
drug or substance that can be identified as having precipitated the bout of acute
hemolysis would have to be avoided from now on. No treatment is available to fix
the genetic defect.
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