Much has changed in the 30 years I have practiced
medicine, though perhaps no change
has been as significant as our collective attitude
toward health. The technological knowledge and
innovations that marked the latter decades of the
20th century have made it possible for us to repair
damaged hearts, cure many forms of cancer, and
even replace diseased organs. Men today can expect
to live a third as long as did their grandfathers.
Epidemiology G6PD deficiency is widely distributed in tropical and subtropical parts of the world (Africa, Southern Europe, the Middle East, Southeast Asia, and Oceania) (Fig. 101-5) and wherever people from those areas have migrated; a conservative estimate is that at least 400 million people have a G6PD-deficiency gene. In several of these areas, the frequency of a G6PD-deficiency gene may be as high as 20% or more.
Peripheral blood smear from a 5-year-old G6PD-deficient boy with acute favism.
A very small minority of subjects with G6PD deficiency have CNSHA of variable severity. The patient is always a male, usually with a history of NNJ, who may present with anemia or unexplained jaundice, or because of gallstones later in life. The spleen may be enlarged. The severity of anemia ranges from borderline to transfusion-dependent. The anemia is usually normo-macrocytic, with
reticulocytosis. Bilirubin and LDH are increased.
Pyrimidine 5'-Nucleotidase (P5N) Deficiency P5N is a key enzyme in the catabolism of nucleotides arising from the degradation of nucleic acids that takes place in the final stages of red cell maturation. How exactly its deficiency causes HA is not well understood, but a highly distinctive feature of this condition is a morphologic abnormality of the red cells known as basophilic stippling. The condition is rare, but it probably ranks third in frequency among red cell enzyme defects (after G6PD deficiency and PK deficiency).
Approach to the Patient: Anemia The evaluation of the patient with anemia requires a careful history and physical examination. Nutritional history related to drugs or alcohol intake and family history of anemia should always be assessed. Certain geographic backgrounds and ethnic origins are associated with an increased likelihood of an inherited disorder of the hemoglobin molecule or intermediary metabolism.
RBC metabolism. The Embden-Meyerhof pathway (glycolysis) generates ATP for energy and membrane maintenance. The generation of NADPH maintains hemoglobin in a reduced state. The hexose monophosphate shunt generates NADPH that is used to reduce glutathione, which protects the red cell
against oxidant stress. Regulation of 2,3-bisphosphoglycerate levels is a critical determinant of oxygen affinity of hemoglobin.