8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

1/15

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

2/15

Glucose-6-phosphate

Dehydrogenase Deficiency

yG6PD Deficiency: an inherited disease

characterized by hemolyticanemiacaused by the inability to detoxify

oxidizing agents.

yMost common disease-producing

enzyme abnormality in humans.

yOver 200 million people.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

3/15

yHas the highest prevalence in theMiddle East, tropical Africa and Asia,and parts of the Mediterranean.

yX-linked

yLife span of individuals is shortenedas a result of complications arising

from chronic hemolysis.y Increased resistance to malaria

shown by female carriers.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

4/15

Note: red blood cell, while biochemically

complex, is a relatively simple cell (no

nucleus, organelles, and protein-synthesizing machinery).

ySo, defects in any of the remaining

components-enzymes, membrane, andhemoglobin-can lead to hemolysis.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

5/15

Pathogenesis ofHemolysis in G6PD

Deficiency

Glutathione: a tripeptide found in

nearly all cells, plays a variety of

roles.

Glutathione (GSH), is its reduced

forms, can chemically detoxify

free radicals.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

6/15

Free radicals: compounds with one or

more unpaired electron shell. Take

electrons from other compounds andare thus very destructive to cell

membranes, proteins, and DNA.

Implicated in cancer, inflammatory

disease, and aging.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

7/15

If the G6PD is missing, it can no longer

convert NADP+to NADPH.

Since NADPH is essential for the

maintenance of the reduced glutathione

pool, glutathione is now oxidized (GS-SG), not reduced (GSH).

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

8/15

No protection against free radicals and

peroxides formed within the cell.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

9/15

Other tissues have alternative sources

ofNADPH production that can keep

glutathione reduced.

The erythrocyte has no nucleus or

ribosomes and can not renew itssupply of the enzyme.

Result: hemolytic anemia

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

10/15

Clinical Symptoms

y Patient may complain of dyspneaor fatigue (caused by anemia)

y Dark urine and, occasionally, backpain may be reported by patients(caused by hemolysis).

y Skin appear jaundiced or pale.

y A resting heartbeat with a flowmurmur may be present if theanemia is pronounced.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

11/15

There are many variations of G6PD

Deficiency - most individuals never

show any clinical manifestations.

Some patients, however, develop

hemolytic anemia if they are

1) treated with an oxidant drug

2) ingest fava beans

3) contact a severe infection

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

12/15

1) Oxidant drugs: commonly used drugs

that produce hemolytic anemia in

patients with G6PD deficiency arebest remembered from the mnemonic

AAA:

Antibiotics (e.g. sulfamethoxazole)Antimalarials (e.g. primaquine)

Antipyretics (e.g. acetanilid)

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

13/15

2) Favism: some forms of G6PDDeficiency are susceptible to the

hemolytic effect of the fava bean,which is a staple in the Mediterraneanregion.

Note: favism is not observed in allindividuals with G6PD Deficiency, butall patients with favism have G6PDDeficiency.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

14/15

3) Infection: most common factor of

hemolysis in G6PD deficiency:

Reaction: infection inflammatory

response free radicals diffuse into

RBC oxidative damage.

8/6/2019 Glucose 6 Phosphatase Dehydrogenase Deficiency

15/15

TreatmentStop taking AAA drugs

Stop eating fava beans

Treat infection promptly