Causes and early diagnosis of vitamin B12 deficiency

Abstract

Introduction: Vitamin B(12) deficiency is widespread. Among the population groups at risk are older people, vegetarians, pregnant women, and patients with renal or intestinal diseases. The neurological symptoms of vitamin B(12) deficiency are unspecific and can be irreversible. Early detection is therefore important, using the most sensitive and specific markers available.

Methods: Selective literature review.

Results and discussion: Total serum vitamin B(12) is a late, relatively insensitive and unspecific biomarker of deficiency. Holotranscobalamin (holoTC), also known as active B(12), is the earliest laboratory parameter for B(12) deficiency, while methyl malonic acid (MMA) is a functional B(12) marker that will increase when the B(12) stores are depleted. Isolated lowering of holoTC shows B(12) depletion (negative B(12) balance), while lowered holoTC plus elevated MMA and homocysteine indicates a metabolically manifest B(12) deficiency, although there still may be no clinical symptoms. The diagnostic use of holoTC allows treatment to be instituted before irreversible neurological damage occurs. As the first clinical manifestations of vitamin B(12) deficiency are unspecific, those at risk should have their B(12) status checked regularly, every two to three years. Because no randomized controlled trials have yet been completed, the diagnostic and therapeutic measures proposed here are merely recommendations.

Keywords: diagnosis; homocysteine; neurological diagnosis; treatment concept; vitamin B12.

Figure1

Transport and cellular absorption of vitamin B12 B12, vitamin B12; TC, transcobalamin II; MS, methionine synthase; Ado, desoxyadenosyl

Figure 2

Algorithm for laboratory diagnosis of vitamin B12 deficiency. (-MMA is the reduction of methyl malonic acid (MMA) concentration subsequent to injections of vitamin B12 by more than 200 nmol/L. (The chart is our own suggestion for the early diagnosis of vitamin B12 deficiency; thus far, no consensus exists to what extent applying the above criteria helps to avoid neurological complications of vitamin B12 deficiency.)