G6PD DEFICIENCY

WHAT IS G6PD DEFICIENCY??? WHAT IS INADEQUATE IN THIS DISEASE??? 

WHAT IS THE FUNCTION OF G6PD??? WHAT IS G6PD??? WHAT IS THE EFFECT???

G6PD deficiency is one of the defective red cell metabolism, where there is deficient in Glucose 6-Phosphate Dehydrogenase (G6PD) enzyme. This is the most common enzyme deficiency seen in the clinical practice. 

The G6PD enzyme is one of the enzyme that involve in the Hexose Monophosphate Shunt (HMP) @ Pentose Phosphate Pathway (PPP). This enzyme function is to reduce NADP (nicotinamide adenine nucleotide phosphate) to NADPH  & oxidise glucose 6-phosphate to 6-phospho-gluconate. The major purpose of this pathway is to generate NADPH & ribulose 5-phosphate, which is for biosynthesis of nucleotide. In red blood cell, this pathway is the only sources of NADPH, because it has no nucleus / ribosome & it cannot renew the supply of the enzyme.

G6PD deficiency is an inherited which characterized by haemolytic anemia. It affecting more than 400 million individuals worldwide. The most affected races are West Africa, the Mediterranean, the Middle East & South East Asia. Severe deficiency occur occasionally in white people. In addition, a family of deficiency i caused by more than 400 different mutation in the gene coding for G6PD. The inheritance is X-linked recessive where it is usually being transmitted from mother to the son. If the mother pass the defect gene to the son, the son will have the disease. In heterozygous female, she will be a carrier for this disease, where she will have normal cell population & G6PD cell population. Homozygous female will manifest the disease.

THE MECHANISM OF THE G6PD IS SHOWN IN DIAGRAM BELOW :

The G6PD enzyme that involve in HMP / PPP is function to produce NADPH from NADP. Then, this NADPH will convert the oxidized glutathione to reduced glutathione. The glutathione function is to maintained the reduced state of sulfhydryl group in protein, including haemoglobin. Besides, it also function as chief red cell antioxidant where it detoxify the hydrogen peroxide.

SO.... if there is deficient of G6PD enzyme, NADPH will not be produce, the, the oxidised glutathione will not be reduced to reduced glutathione, where it act as antioxidant. As a result, there'll be accumulation of hydrogen peroxide which is a type of free radical that can damage the red blood cell.

4 CLINICAL CONDITION ASSOCIATE WITH G6PD DEF. :

1. Acute Haemolytic Anemia

2. Favism

3. Neonatal Jaundice

4. Congenital Nonspherocytic Anemia

1. Acute Haemolytic Anemia

-occur when expose to certain drug / infection
-in drug induce process / infection induces haemolytic process, patients will experience,:

• nausea
• abdominal pain
• rapid decrease hematocrit within 24- 48 hour
• haemoglobinuria

Agent that can cause acute haemolytic anemia :

Antimalarials drug (primaquine, pamaquine, chloroquine, fansidar, maloprim)

Salphonamides & Salphones

Antibacterial agents (chloramphenicol, nitrofurans)

Analgesics (aspirin)

Antihelminths 

Naphthalene (montballs)

2. Favism
-usually found in individual with G6PD Mediterrenean & Canton
-hour after ingesting fava beans / broad beans, patient will experience :

• irritable & lethargic
• fever
• nausea
• abdominal pain
• haemoglobinuria within 48 hours

3. Neonatal Jaundice
-within 2 / 3 days after birth
-show more jaundice than anemia
-early management is urgent! to prevent kernicterus in infant

4. Congenital Nonsperocytic Anemia
-have history of NNJ complicated by gallstones, enlarge spleen / both

TREATMENT:

Stopped the drug, Treat underlying infection, Blood transfusion (severe), Phototherapy (NNJ)

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