Folate deficiency classically presents as megaloblastic anaemia, with absence of neurological signs.
Common causes include malabsorption, drugs and toxins, states of increased demand, and dietary deficiency. Hereditary folate malabsorption and other inborn errors of folate metabolism are rare causes.
In early disease, haemoglobin and mean corpuscular volume are normal. In severe disease, patients present with symptomatic anaemia and pancytopenia.
Maternal folate deficiency is associated with fetal neural tube defects (NTDs).
Diagnosis is confirmed by the presence of low serum folate and/or low red blood cell folate. Elevated plasma homocysteine levels are helpful in situations of diagnostic difficulty.
Vitamin B12 (cobalamin) deficiency must be ruled out before initiating folic acid therapy, as the therapy may mask neurological manifestations of underlying vitamin B12 deficiency.
Oral folic acid is usually considered sufficient therapy. Underlying cause should be identified and treated.
Food fortification programmes instituted in some countries have decreased the incidence of folate deficiency and associated anaemia and fetal NTDs.
Megaloblastic anaemia without neuropathy is the classic manifestation of folate deficiency.
Folate, also known as vitamin B9, is present in green vegetables, legumes, and some fruits.
Deficiency arises due to malabsorption, drugs and toxins, increased demand, or dietary deficiency.
History and exam
Key diagnostic factors
- presence of risk factors
Other diagnostic factors
- prolonged diarrhoea
- loss of appetite and weight loss
- shortness of breath
- heart murmur
- signs of heart failure
- signs of chronic alcohol misuse
- signs of haemolytic anaemia
- signs of exfoliative dermatitis
- painful swallowing
- angular stomatitis
- neurological deficits in children
- low dietary folate intake
- age >65 years
- alcohol-use disorder
- pregnant or lactating
- intestinal malabsorptive disorders
- use of trimethoprim, methotrexate, sulfasalazine, pyrimethamine, or anticonvulsants (e.g., phenytoin, phenobarbital)
- infantile intake of goats' milk
- congenital defects in folate absorption and metabolism
- states of increased cell turnover
- intake of special diet
- chronic dialysis
1st investigations to order
- peripheral blood smear
- reticulocyte count
Investigations to consider
- serum folate
- red blood cell folate
- serum vitamin B12
- serum LDH
- serum unconjugated bilirubin
- serum iron panel
- plasma or serum methylmalonic acid
- plasma homocysteine
- bone marrow aspirate/biopsy
at risk of folate deficiency due to pregnancy or lactation
at risk of folate deficiency due to malabsorption disorders, chronic haemolytic disorder, or chronic dialysis
at risk of folate deficiency due to medication
acquired: macrocytosis without anaemia
acquired: macrocytic anaemia and pancytopenia
congenital folate metabolism defects
congenital folate malabsorption
congenital cerebral folate transport deficiency
- Vitamin B12 (cobalamin) deficiency
- Thiamine-responsive megaloblastic anaemia
- Hereditary orotic aciduria
- Antenatal care
- Folic acid supplementation for the prevention of neural tube defects
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