53 Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency

Michelle To and Valentin Villatoro

Normal G6PD Function: Hexose Monophosphate (HMP) Shunt and Oxidative Damage1,2

The HMP Shunt describes the glycolytic pathway where glucose is transferred to and catabolized in the cell to produce ATP and maintain sustainable amounts of reduced glutathione (GSH). GSH acts to protect the red blood cell from oxidative damage by reducing oxidative molecules (Peroxides and free oxygen radicals) and becoming oxidized itself.

 

In the HMP shunt, NADPH is generated by G6PD from NADP which than acts to regenerate reduced glutathione from its oxidized state to allow continued protection from oxidative damage. A lack of G6PD results in increased red blood cell destruction.

 

G6PD activity is highest in younger cells (i.e. reticulocytes) compared to that of older and more mature red blood cells.1

 

Mutation:2

G6PD gene mutation results in decreased G6PD levels.

 

Inheritance:1

X-linked

 

Complications:1,2

Acute hemolytic Anemia

Neonatal Hyperbilirubinemia

Chronic Nonspherocytic Hemolytic Anemia

 

Causes of Hemolytic Episodes:1,2

Exposure to oxidative agents:

-Drugs (e.g. antimalarials, sulfonamides)

-Infections

-Fava Beans (Favism)

 

Notes:

G6PD deficiency is commonly associated with bite and blister cells. Oxidized hemoglobins become denatured and form heinz bodies within the red blood cells. These heinz bodies can be removed by splenic macrophages through a “pitting” mechanism, which results in the formation of bite and blister cells.1

 

It has been suggested that G6PD deficiency acts as a protective mechanism from malaria as the prevalence of G6PD deficiency coincides with that of malaria.1

 

Laboratory Results for G6PD Deficiency:1

CBC:

WBC: Increased

PLT: Normal

Hb: Decreased

MCHC: Increased

RETIC: Increased

PBS:

Bite and Blister  Cells

Polychromasia

Occasional spherocytes

Heinz bodies (Supravital staining)

Other Tests:

Dye Reduction Test: No colour change

G6PD Assay: Decreased activity

DAT: Negative

 

Hemolysis Markers:

Indirect Bilirubin: Increased

LDH: Increased

Haptoglobin: Decreased

Hemoglobinemia

Hemoglobinuria


References:

1. Lake M, Bessmer D. Hemolytic anemia: enzyme deficiencies. In: Clinical laboratory hematology. 3rd ed. New Jersey: Pearson; 2015. p. 334-47.

2. Keohane EM. Intrinsic defects leading to increased erythrocyte destruction. In: Rodak’s hematology clinical applications and principles. 5th ed. St. Louis, Missouri: Saunders; 2015. p. 367–93.

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A Laboratory Guide to Clinical Hematology by Michelle To and Valentin Villatoro is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, except where otherwise noted.

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