Topic 5 - Vitamin B12 and folate metabolism disorders

Question 1

What type of anaemia does Vitamin B12 deficiency cause?

Answer 1

Megaloblastic anaemia

Question 2

What is Megaloblastic anaemia?

Answer 2

it is a group of disorders characterized by defective nuclear maturation
caused by impaired DNA synthesis, causing a decreased no. of cellular
divisions and hence larger cells.

Megaloblasts and large and abnormal red cell precursors and will be seen in the bone marrow.
Macro-ovalocytes will be seen in PBF
There will be larger granulocyte precursors with giant metamyelocytes, a
striking feature.

Question 3

What is the biochemical aspect of Vit B12 and folate?

Answer 3

❖ Vit B12 & folic acid function as cofactors in DNA synthesis.
❖ Deficiency interferes with nuclear maturation, DNA replication and
cell division.
❖ Drugs that interfere with metabolism of above vitamins also cause
DNA impairment

Question 4

What are the clinical manifestations of megaloblastic anaemia?

Answer 4

❖ Anaemia (mild to severe): pallor
❖ Symptoms: weakness, fatigue, shortness of breath
❖ Congestive heart failure -/+ (depending upon the degree of
anaemia)
❖ Lemon-yellow skin tint (mild jaundice)

Question 5

What will the bone marrow morphology be for megaloblastic anaemia?

Answer 5

❖ Hypercellular
❖ Low Myeloid : Erythroid ratio (1:1 to 1:3) (normal M:E is 4:1)
❖ Megaloblasts
▪ Large abnormal red cell precursors with increased RNA per
DNA unit
▪ Cytoplasm maturation is normal
❖ Giant bands & metamyelocytes

Question 6

What will the PBF morphology be for megaloblastic anaemia?

Answer 6

❖ Macrocytic normochromic anaemia
❖ MCV: 100 to 160 fL
❖ MCH is elevated, MCHC is normal
❖ Hb: normal to low
❖ RBC count : decreased
❖ Decreased reticulocytes
❖ WBC: normal to low : 2 to 4x109
/L (4–10 x 109
/L)
❖ Platelets: normal to low < 100 x 109
/L (in severe anaemia) (150 –
450 x 109
/L)