Diagnosis of megaloblastic anaemias
Wickramasinghe SN.
Department of Haematology, Faculty of Medicine, Imperial College, St Mary's Campus, Praed Street, London W2 1PG, UK.

There are a large number of causes of megaloblastic anaemia. The most frequent are disorders resulting in vitamin B(12) or folate deficiency. The diagnostic process often consists first of establishing the presence of B(12) or folate deficiency and then of determining the cause of deficiency. The blood count, blood film, serum B(12) assay, and red cell and serum folate assays are the primary investigations. Other useful investigations include serum/plasma methylmalonic acid (MMA), plasma total homocysteine (tHCYS) and serum holo-transcobalamin II assays. All currently used tests have limitations regarding specificity or sensitivity or both and the metabolite assays are not widely available. An understanding of these limitations is essential in formulating any diagnostic strategy. The wide use of serum B(12) and metabolite assays has resulted in the increasingly early diagnosis of B(12) deficiency, often in patients without B(12)-related symptoms (subclinical deficiency). Food cobalamin malabsorption is the most frequent cause of a low serum B(12). At least 25% of low serum B(12) levels are not associated with elevated metabolite levels and may not indicate B(12) deficiency. Some of these are caused by partial deficiency of transcobalamine I.

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