Folate Deficiency

Deficiency of folic acid (vitamin B9), essential for one-carbon metabolism, purine and thymidylate synthesis, and DNA replication, producing megaloblastic anaemia clinically similar to B12 deficiency but without the neurological consequences, since folate is not required for myelin maintenance.

Causes

• Dietary insufficiency: body stores are small (roughly 3-4 months' supply), so deficiency develops faster than B12 deficiency with inadequate intake --- poor diet, alcoholism, elderly living alone, institutionalised patients.
• Malabsorption: coeliac disease, tropical sprue, extensive small bowel disease or resection.
• Increased requirement: pregnancy and lactation, haemolytic anaemia (increased cell turnover), malignancy, chronic exfoliative skin disease, and renal dialysis (folate is dialysable).
• Drugs: methotrexate (folate antagonist), trimethoprim, phenytoin, sulfasalazine, and alcohol (both reduces intake and impairs absorption/metabolism).

• Fatigue, pallor, dyspnoea --- identical general anaemia symptoms to B12 deficiency.
• Glossitis and angular cheilitis.
• No neurological features attributable to folate deficiency itself; any neuropathy in a folate-deficient patient should prompt evaluation for coexisting B12 deficiency.
• In pregnancy, maternal folate deficiency is strongly associated with neural tube defects in the fetus, which is the basis for universal periconceptional supplementation.
• Symptoms of the underlying cause: diarrhoea and weight loss in malabsorption, alcohol dependence features.

• Full blood count: macrocytic anaemia, indistinguishable from B12 deficiency on indices alone.
• Blood film: hypersegmented neutrophils, oval macrocytes.
• Serum or red cell folate (red cell folate is a more reliable indicator of tissue stores, less affected by recent dietary intake than serum folate).
• Elevated homocysteine with normal methylmalonic acid distinguishes isolated folate deficiency from B12 deficiency (where both are elevated).
• Always check B12 concurrently before treating, since giving folic acid to a patient with unrecognised B12 deficiency can correct the anaemia while allowing subacute combined degeneration to progress unchecked.
• Investigate the cause: coeliac serology, alcohol history, medication review, dietary assessment.

• Folic acid 5mg orally daily, typically for 4 months or until full haematological recovery; longer or indefinite in ongoing increased demand (chronic haemolysis, dialysis) or malabsorption.
• Confirm B12 is normal or being replaced concurrently before starting folic acid, without exception.
• Periconceptional folic acid 400 micrograms daily (5mg in high-risk women --- epilepsy on certain antiepileptics, diabetes, obesity, previous neural tube defect pregnancy, malabsorption) from before conception through the first trimester for neural tube defect prevention.
• Address the underlying cause: nutritional counselling, alcohol cessation support, treatment of coeliac disease or malabsorptive conditions.
• Monitor reticulocyte response (rises within days) and haemoglobin normalisation over weeks.