Early detection of vitamin B₁₂ deficiency depends on biochemical measurements. Lindenbaum and colleagues (1990) reported that metabolites that arise from B₁₂ insufficiency are more sensitive indicators of B₁₂ deficiency than is the serum B₁₂ value. This was found in patients with pernicious anemia or previous gastrectomy who experienced early hematological relapse: serum methylmalonic acid (MMA), total homocysteine, or both were elevated in 95 percent of the instances of relapse whereas the serum B₁₂ value was low (less than 150 pmol/L [200 pg/mL]) in 69 percent. Similarly, serum B₁₂ was found to be an insensitive indicator in a review of records of patients with clinically significant B₁₂ deficiency. Five deficient individuals had neurological disorders that were responsive to B₁₂ and had elevated serum MMA and homocysteine values even though their serum B₁₂ values were greater than 150 pmol/L (200 pg/mL) and anemia was absent or mild. In a recent series of 173 patients, 5.2 percent of those with recognized B₁₂ deficiency had serum B₁₂ values in the normal range. Similar findings were reported elsewhere (e.g., Carmel, 1988; Pennypacker et al., 1992; Stabler et al., 1996). At present, the techniques developed to measure serum MMA and homocysteine (capillary gas chromatography and mass spectrometry) are costly and may be beyond the scope of routine laboratories. Conditions that may warrant assessment of B₁₂ status because they may result in B₁₂ deficiency are summarized in Table 9-4.