Megaloblastic anaemia

The megaloblastic anaemias are characterised by delayed maturation of the nucleus of red cells in the bone marrow due to defective synthesis of DNA. Red cells either die in the marrow (‘ineffective haematopoiesis’) or enter the bloodstream as enlarged, misshapen cells with a reduced survival time. In clinical practice megaloblastic anaemia is almost always caused by deficiency of vitamin B₁₂ (cobalamin) or folate (pteroylmonoglutamate). It is one of the most common causes of a macrocytic anaemia.

Why does deficiency of vitamin B₁₂ or folate lead to megaloblastic anaemia?

Key characteristics of these essential vitamins are summarised in Table 13.1.

Table 13.1

Vitamin B₁₂ and folate

Characteristic	Vitamin B₁₂	Folate
Average dietary intake/day (µg)	20	250¹
Minimum adequate intake/day (µg)	1–2	150¹
Major food sources	Animal produce only	Liver, vegetables
Normal body stores	Sufficient for several years	Sufficient for a few months
Mode of absorption	Combined with transport protein (IF) secreted by gastric parietal cells – then absorbed through ileum via special receptors	Dietary folate converted to methyl THF and absorbed in duodenum and jejunum

THF: tetrahydrofolate; IF: intrinsic factor.

¹ 500 µg daily required in pregnancy.

Both folate and vitamin B₁₂ are necessary for the synthesis of DNA (Fig 13.1). Folate is needed in its tetrahydrofolate form (FH₄) as a cofactor in DNA synthesis. Deficiency of B₁₂ leads to impaired conversion of homocysteine to methionine causing folate to be ‘trapped’ in the methyl form. The resultant deficiency in methylene FH₄ deprives the cell of the coenzyme necessary for DNA formation.