G6PD Deficiency and its Effects

Study Notes

G6PD deficiency resulted in 4,100 deaths in 2013 and 3,400 deaths in 1990.
The primary results of the pentose phosphate pathway are:
- Generation of reducing equivalents (NADPH) used in reductive biosynthesis reactions.
- Production of ribose 5-phosphate (R5P) used in the synthesis of nucleotides and nucleic acids.
- Production of erythrose 4-phosphate (E4P) used in the synthesis of aromatic amino acids.
G6PD is necessary for maintaining adequate levels of glutathione (GSH) for reducing cellular oxidants.
In G6PD deficiency, hemoglobin is oxidized to methemoglobin, leading to its denaturation and precipitation in the form of Heinz bodies.
Heinz bodies attach to the erythrocyte membrane, causing cell rigidity and removal by splenic macrophages, producing bite cells.
Oxidation of membrane proteins and lipids leads to disruption of membrane integrity, causing cell membrane damage and intravascular hemolysis.
Heinz bodies are formed by damage to the hemoglobin component molecules, usually through oxidant damage or inherited mutations.

Blister cells appear as red blood cells containing a peripherally located vacuole.
Heinz bodies are formed by the denaturation and precipitation of hemoglobin, leading to cell damage and premature cell lysis.

Assay for G6PD should be performed 2-3 months after a hemolytic episode, when enzyme activity is nearly normal.
Diagnosis during or shortly after a hemolytic episode can be made by testing older dense erythrocytes at the bottom of the blood column.
In acute hemolytic episodes, blood transfusion may be necessary, and removal of the oxidizing agent (drug or fava bean) is required.
Prevention involves avoiding exposure to oxidizing agents and consumption of fava beans.

A 17-year-old healthy young man took 30 grams of Optalgin (dipyrone) in an attempt to commit suicide, resulting in a G6PD deficiency case.

Autoimmune hemolytic anemias (AIHAs) are caused by antibody production against the body's own red cells.
AIHAs are characterized by a positive direct antiglobulin test (DAT) and divided into 'warm' and 'cold' types.
Laboratory identification of sensitized red cells involves agglutination in saline and antihuman globulin (AHG) tests.

The complement system is a part of the immune system that enhances the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism.
The complement system is made up of a large number of distinct plasma proteins that react with one another to opsonize pathogens and induce inflammatory responses.

Requirements: About 3-5 mcg of cobalamin per day is needed to maintain normal biochemical functions.
Cobalamin stores are sufficient to provide the normal daily requirement for about 1,000 days.
Elevated Hcy-MMA levels are associated with irreversible neurological deterioration, neural tube defects, anemia, renal dysfunction, and long-term adverse effects.

Aplastic anemia (AA) is a hematologic disorder characterized by pancytopenia on peripheral blood smear and a markedly hypocellular or acellular marrow (aplasia).
AA represents approximately one-third of all pediatric lymphomas occurring outside Africa.

Burkitt lymphoma often involves extranodal sites, especially in the jaw in Africa and the abdomen in non-African cases.
The presence of the MYC-associated translocation [t(8;14) MYC/Immunoglobulin heavy chain gene (IGH)] or variants is necessary to confirm all but the most classic cases.
A biopsy of Burkitt lymphoma usually reveals a diffuse infiltrate of neoplastic cells demonstrating a “starry sky” appearance.

Tingible body macrophages (TBMs) are a type of macrophage found in germinal centers, containing many phagocytized, apoptotic cells in various states of degradation.
Tingible body macrophages contain condensed chromatin fragments.

Mantle lymphoma is an aggressive type of lymphoma resulting from chromosomal translocation (14,11).
BCL-1 gene is placed next to Ig promoter, encoding the protein Cyclin D1, which stimulates cell growth and division.