Makindo Medical Notes

Folate should be given to anyone in early pregnancy or planning pregnancy

About

• Folic acid fortification in flour is mandatory in the UK to prevent Neural tube defects in babies.
• Folate, a B vitamin, is present in natural foods such as green vegetables, legumes, and some fruits.

Aetiology

• Folate stores last 4 months but deficiency may develop rapidly in patients who have both a poor intake
• Folates are absorbed in the terminal ileum and almost 50% is stored in the liver.
• Folate is essential for DNA synthesis.
• Clinical signs of deficiency are seen first in rapidly turning over cells such as in the bone marrow and gastrointestinal tract leading to megaloblastic anaemia and glossitis.

Causes

• Malabsorption (eg, coeliac disease, tropical sprue, congenital specific malabsorption, jejunal resection, inflammatory bowel disease).
• Diet: Poor intake, Old age, poor social conditions, Malnutrition, Alcohol excess (also causes impaired utilisation), Poor intake due to anorexia. Food fads.
• Excessive requirements: Physiological (e.g. pregnancy, lactation, prematurity and infancy). Malignancy (e.g. leukaemia, carcinoma, lymphoma). Blood disorders (e.g. haemolytic anaemias, sickle cell anaemia, thalassaemia major, chronic myelosclerosis). Inflammation (e.g. tuberculosis, Crohn's disease, malaria).
• Metabolic (e.g. homocystinuria).
• Haemodialysis or peritoneal dialysis.
• Excessive urinary excretion
• Antifolate drugs e.g. anticonvulsants and possibly alcohol and nitrofurantoin).
• Malabsorption of folate (e.g. cholestyramine, sulfasalazine, methotrexate). Trimethoprim may exacerbate pre-existing folate deficiency but does not cause megaloblastic anaemia.
• Genetic disorders: Mutations in the SLC46A1 gene, leading to proton-coupled folate transporter deficiency.[4]

Clinical

• Macrocytic anaemia, Glossitis can occur.
• Paraesthesia, numbness, peripheral neuropathy or psychiatric disturbance (e.g. depression).

Differentials

• Vitamin B12 deficiency.
• Macrocytosis: Pregnancy. Alcohol excess. Liver disease. Reticulocytosis. Hypothyroidism.
• Aplastic anaemia, sideroblastic anaemia, pure red cell aplasia.

Investigations

• FBC and blood film: features of megaloblastic anaemia
• Mean corpuscular volume (MCV) > 96 fL. Hypersegmented polymorphs with six or more lobes in the nucleus. If severe, there may be leukopenia and thrombocytopenia.
• Folate level: serum folate lower than 7 nmol/L (3 lg/L) as a guideline because the risk of megaloblastic anaemia greatly increases below this level. However, Serum folate levels are affected by recent folate intake giving false reassurance. Serum folate is reduced in the immediate post renal dialysis period so should not be measured at these times. Medications including anticonvulsants lower the serum folate level.
• Check Vitamin B12 levels so can be replaced if low
• Red cell folate level indicator of longer-term folate status than the serum folate assay.

Management

• Folate 5 mg of folic acid daily for four months for adults (until the term in pregnant women)
• Folate 15 mg daily may be required in malabsorption states.
• Any underlying cause - eg, coeliac disease - should be treated
• Ensure replace B12 if low or subacute combined degeneration of cord if a low B12 not replaced at the same time.

References

Revisions