glycolytic cause of haemolytic anaemia

1. DEFICIENCIES OF GLYCOLYTIC ENZYMES AS A CAUSE OF HAEMOLYTIC
ANAEMIA.
A SEMINAR PRESENTATION
BY
OBINNA MOSES IKE
ADMISSION NO: 1511222058
TO THE DEPARTMENT OF HAEMATOLOGY, SCHOOL OF MEDICAL
LABORATORY SCIENCES, USMANU DANFODIYO UNIVERSITY,
SOKOTO
SUPERVISED BY
MALAMA HAUWA BUHARI ALI
JUNE, 2021

2. TABLE OF CONTENT
 Introduction
 Causes of haemolytic anaemia
 Classification of haemolytic anaemia
 G6PD
 Pyruvate Kinase deficiency
Epidemiology of pyruvate kinase
Etiology of pyruvate Kinase
 General Symptoms of haemolytic anaemia
 Laboratory Diagnosis
 Laboratory findings
 Conclusions
 References

3. INTRODUCTION
• Hemolytic anemia is is the destruction of red blood cells (RBCs)
before their normal 120-day life span (mentzer and schrir, 2018).
• It is also a form of anemia due to hemolysis, the abnormal
breakdown of red blood cells (RBCs), either intravascular hemolysis
or extravascular hemolysis
• It has numerous possible consequences, ranging from general
symptoms to life-threatening systemic effects.
(Capriotti and Theresa, 2016)

4. CAUSES OF HAEMOLYTIC ANAEMIA
• They may be classified according to the means of hemolysis, being
either intrinsic in cases where the cause is related to the red blood
cell (RBC) itself, or extrinsic in cases where factors external to the
RBC dominate ( Stephen et al.,2009)
• Intrinsic causes
1. Red blood cell membrane defect e.g Hereditary spherocytosis
2. Defect in hemoglobin production e.g Sickle cell Anaemia
3. Defective red blood cell metabolism e.g G6PD
(Capriotti and Theresa ,2016)

5. CAUSES OF HAEMOLYTIC ANAEMIA CONT’D
• Extrinsic
1. Autoimmume
2. Alloimmune
3. Renal Disease
4. Infection
( Capriotti and Theresa ,2016)

6. CLASSIFICATION OF HAEMOLYTIC
ANAEMIA
• 1. INTRACORPUSCULAR HEMOLYSIS
– Membrane Abnormalities
– Haemoglobin defects
– Enzyme defects
• 2. EXTRACORPUSCULAR HEMOLYSIS
– Nonimmune
– Immune
( Stanley et al.,2017).

7. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the
most common RBC enzyme disorder in the world, affecting
approximately 330 million people worldwide(Nkhoma et
al.,2008).
• G6PD is a key enzyme in the pentose phosphate pathway;
deficiency in this enzyme leads to inadequate levels of NADPH .
(Luzzatto et al., 2016).

8. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY CONT’D
Figure 1 Biochemical pathway of glucose-6-phosphate dehydrogenase (Jennifer et al .,2005)

9. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY CONT’D
• G6PD deficiency is an X-linked recessive disorder, with an inheritance pattern
similar to that of hemophilia.
• Males usually manifest the abnormality and females are carriers (Prchalet al.,
2020).
Figure 2 Inheritance pattern in G6PD (Luzzato,1969)

10. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY CONT’D
 FACTORS THAT TRIGGER G6PD DEFIENCY IN HAEMOLYTIC
ANAEMIA
 Anti- malaria e.g Quinine
 Some antibiotics e.g Chloramphenicol )
 Fava Beans
Figure3 showing the picture of fava beans ( Etstratia , 2020)

11. GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY CONT’D
 G6PD VARIANTS
• G6PD deficiency is divided into class variants based on severity.
• Class I is rare but results in chronic non-spherocytic haemolytic anemia which
worsens with exposure to oxidant stress (<10% normal enzyme activity).
• Class II has episodic severe hemolysis with oxidant stress (<10% normal enzyme
activity).
• Class III variants experience moderate hemolysis with exposure to oxidant
triggers (10–60% normal enzyme activity).
((Cappellini and Fiorelli,2008)

12. PYRUVATE KINASE DEFICIENCY
• Red cell pyruvate kinase deficiency (PKD) is the most common
glycolytic defect causing congenital non-spherocytic haemolytic
anemia.
• Pyruvate kinase converts phosphoenolpyruvate to pyruvate, creating
50% of the red cell total ATP.
• Red cell longevity is dependent on the ATP produced in glycolysis.
• Thus, PKD leads to less ATP and a shortened red cell lifespan.
(Grace et al., 2015).

13. EPIDEMIOLOGY OF PYRUVATE KINASE
• Most frequent enzyme abnormality of the glycolytic pathway.
• Most common cause of hereditary nonspherocytic haemolytic
anaemia.
• Estimated prevalence:1 in 20,000 Global districbution
(Beutler et al., 2000)

14. ETIOLOGY OF PYRUVATE KINASE
• PKD is caused by a mutation in PKLR gene located on
chromosome 1q21.
• More than 200 mutations in the PK-LR gene have been
reported.
• PKD is inherited as an autosomal recessive disorder.
(Beutler et al., 2000)

15. GENERAL SYMPTOMS OF HAEMOLYTIC
ANAEMIA
• Paleness of the skin
• Fatigue
• Fever
• Confusion
• Lightheadedness
• Dizziness
• Weakness or inability to do physical activity
• Dark urine
• Yellowing of the skin and the whites of the eyes (jaundice)
(Capriotti and Theresa ,2016)

16. LABORATORY DIAGNOSIS
• Complete Blood Count
• Reticulocyte count
• Peripheral smear
• serum bilirubin
• PKLR gene molecule analysis
• Direct enzyme essay
• Haptoglobin level
(Zanella et al., 2007)

17. LABORATORY FINDINGS
• High level of Haemoglobin
• Reticulocytosis
• Reduce haptogloglobin concentration
(Zanella et al., 2007)

18. CONCLUSION
• Deficiency of glycolytic enzymes is one of the major causes of
hemolytic anemia in Adult and children.
• This is as a result of mutations in G6PD genes or mutation of PKLR
gene, which result to deficiency of pyruvate kinase and G6PD
enzymes along the glycolytic pathways.
• This lead to deformability and dysfunction of red cells, which will
result to hereditary non-spherocytic haemolytic anaemia.

19. SOME CITED REFERENCES
Cappellini, M., Fiorelli G. ( 2008). Glucose-6-phosphate dehydrogenase
deficiency. Lancet. ;371(9606):64–74.
Grace, RF., Glader B.(2018). Red blood cell enzyme disorders. Pediatric
Clinic North America journal ;65(3):579–95.
Luzzatto, L., Nannelli C, Notaro R.(2016). Glucose-6-phosphate
dehydrogenase deficiency. Hematology Oncology Clinic North
America Journal. ;30(2):373–93.
Zanella, A., Bianchi P. (2007). Red cell pyruvate kinase deficiency: from genetics to
clinical manifestations. Baillieres Best Practice Response Clinical
Haematology ;13(1):57–81.

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