Diagnosis of megaloblastic anaemias

Summary 

There are a large number of causes of megaloblastic anaemia. The most frequent are disorders resulting in vitamin B₁₂ or folate deficiency. The diagnostic process often consists first of establishing the presence of B₁₂ or folate deficiency and then of determining the cause of deficiency. The blood count, blood film, serum B₁₂ 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 B₁₂ and metabolite assays has resulted in the increasingly early diagnosis of B₁₂ deficiency, often in patients without B₁₂-related symptoms (subclinical deficiency). Food cobalamin malabsorption is the most frequent cause of a low serum B₁₂. At least 25% of low serum B₁₂ levels are not associated with elevated metabolite levels and may not indicate B₁₂ deficiency. Some of these are caused by partial deficiency of transcobalamine I.

Keywords: Megaloblastic anaemia, Diagnosis, B₁₂ deficiency, Folate deficiency, Inborn errors of metabolism