Define Megaloblastic Anaemia. Describe its causes, clinical features, investigations and diagnosis.

Definition

• Megaloblastic anaemia is a macrocytic anaemia caused by deficiency of vitamin B12 or folate, which impairs DNA synthesis.
• This produces large, immature red-cell precursors (megaloblasts) and ineffective erythropoiesis.

Causes

• Vitamin B12 — inadequate intake (strict vegetarian diet; infants breastfed by a B12-deficient mother), malabsorption (pernicious anaemia, ileal disease).
• Folate — poor intake (goat's milk, overcooked food), increased demand (haemolysis, rapid growth), malabsorption, and drugs (methotrexate, phenytoin).

Clinical Features

• Pallor, fatigue, glossitis and mild jaundice; skin hyperpigmentation.
• Neurological features with B12 deficiency — developmental regression, irritability, hypotonia in infants (and subacute combined degeneration in older patients).
• Severe cases → pancytopenia.

Investigations & Management

• Macrocytic anaemia (high MCV); blood film — macro-ovalocytes and hypersegmented neutrophils; marrow shows megaloblasts.
• Low serum B12 and/or folate.
• Replace the deficient vitamin — B12 (usually intramuscular) or oral folic acid; treat the underlying cause; correct diet.

Differential Diagnosis

• Other causes of macrocytosis — hypothyroidism, liver disease, aplastic anaemia, reticulocytosis.
• Combined iron + B12/folate deficiency (a 'dimorphic' picture with a normal MCV).

Prevention

Ensure adequate maternal B12/folate in pregnancy and lactation, dietary diversification, and folic-acid supplementation in situations of increased demand (haemolysis, prematurity, rapid growth).

Give B12 before folate to avoid worsening neurological damage.