Problems with the serum vitamin B12 assay

Area of Science:

• Clinical Chemistry
• Hematology
• Nutritional Science

Background:

• Serum vitamin B12 estimations show significant inter-laboratory variability in routine practice.
• Current assays are often insensitive and non-specific for diagnosing vitamin B12 deficiency.
• The correlation between serum vitamin B12 levels and the clinical/biochemical consequences of deficiency is poor.

Purpose of the Study:

• To investigate the limitations of serum vitamin B12 assays in diagnosing deficiency.
• To explore the role of vitamin B12 binding proteins in serum.
• To identify more reliable indicators of vitamin B12 status.

Main Methods:

• Analysis of quality control trial data for serum vitamin B12 assays.
• Review of existing literature on vitamin B12 metabolism and binding proteins.
• Comparison of serum vitamin B12 levels with clinical manifestations of deficiency.

Main Results:

• Serum vitamin B12 assays exhibit substantial variability, leading to diagnostic confusion.
• The majority of cobalamin in human serum is bound to transcobalamin I, a non-metabolically active protein.
• Deficiency of transcobalamin II can cause megaloblastic anemia despite normal serum vitamin B12 levels.

Conclusions:

• Serum vitamin B12 levels are an unreliable sole criterion for diagnosing vitamin B12 deficiency.
• The binding pattern of vitamin B12 in serum complicates accurate assessment.
• Transcobalamin II deficiency highlights the inadequacy of total serum cobalamin as a diagnostic marker.