Why Vitamin B12 Deficiency Should be on your Radar Screen

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<strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong> <strong>be</strong>cause cobalamin is required to convert methylmalonyl coenzyme A to succinyl coenzyme A.(2) In one study, 98.4% of people with a vitamin <strong>B12</strong> level less than 200 pg/mL also had elevated MMA levels (defined as values more than 376 nanomoles per liter [nmol/L]).(70) Note that false-positive increases in serum MMA have <strong>be</strong>en identified among patients with impaired renal function. It is necessary to rule out whether your patient has either marked intravascular volume depletion or renal insufficiency when interpreting the MMA level, especially in the absence of a low cobalamin level.(70) Elevated MMA levels among most patients indicate tissue depletion of vitamin <strong>B12</strong>. Data from the National Health and Nutrition Examination Survey (NHANES) 2001–2004 in Table 4 shows the prevalence of vitamin <strong>B12</strong> deficiency using combinations of serum <strong>B12</strong> levels and MMA levels. Table 4. Prevalence of National Health and Nutrition Examination Survery Participants With Biochemically Defined <strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong>* By Age Group, United States, 2001–2004 Age Group <strong>B12</strong> ≤ 200 <strong>B12</strong> > 200 pg/mL (Years of Age) pg/mL and MMA and MMA ≥ 270 ≥ 270 nmol/L nmol/L 9–13 years of age 0.1% 2.5% 14–18 years of age 0.2% 3.7% 19–30 years of age 0.4% 3.5% 31–50 years of age 0.6% 3.6% ≥ 51 years of age 1.6% 7.9% *Biochemically defined vitamin <strong>B12</strong> deficiency is serum <strong>B12</strong> ≤ 200 picograms per milliliter (pg/mL) and methylmalonic acid (MMA) ≥ 270 nanomoles per liter (nmol/L) or serum <strong>B12</strong> > 200 pg/mL and MMA ≥ 270 nmol/L Two popular methods for interpreting diagnostic thresholds for MMA and Hcy elevations are the use of cutpoints determined by laboratory norms (e.g., 3 standard deviations above the mean) and specific values (e.g., MMA greater than 0.26 micromole per liter 31 Conversions 1,000 nmol/L* = 1 µmol/L† 376 nmol/L = 0.376 µmol/L *nanomols per liter †micromols per liter
<strong>Vitamin</strong> <strong>B12</strong> <strong>Deficiency</strong> [µmol/L](69) or greater than 0.4 µmol/L;(59) Hcy greater than 15 µmol/L(71, 72)). Many clinicians rely on ranges specified by the clinical laboratories they use. The cost of testing for MMA or Hcy might <strong>be</strong> a concern. Quotes from Quest Laboratories (Atlanta, Georgia, May 2006) state that the direct patient (no insurance) cost for a serum MMA is $212 and for a serum Hcy is $191. Other metabolites, serum propionate and serum 2methylcitrate, are also present in vitamin <strong>B12</strong> deficiency. However, measuring either of these metabolites has no advantage over measuring MMA to diagnose a vitamin <strong>B12</strong> deficiency,(2) and they are not available routinely in many clinical laboratories. Again, it is important to remem<strong>be</strong>r that abnormal metabolite levels might <strong>be</strong> due to conditions other than a vitamin <strong>B12</strong> deficiency, such as renal insufficiency. In one study of the elderly, renal insufficiency was associated with 20% or greater of all abnormal metabolite levels.(11) Other Tests If the root cause of vitamin <strong>B12</strong> deficiency is not obvious, you should consider ordering additional tests to determine it. Antibodies to intrinsic factor and gastrin or pentagastrin I levels are often used to diagnose pernicious anemia.(10, 36, 60) Serum holotranscobalamin II measures one of the bloodbinding proteins used to transport vitamin <strong>B12</strong>.(60) Some investigators recommend it;(73) others are concerned about the lack of convincing evidence of its value.(2, 9, 10, 60) Theoretically, it is attractive, but early claims of its value have <strong>be</strong>en poorly documented. While immunoassays have replaced the older crude methods, it is too early to determine whether measurement of holotranscobalamin II is <strong>be</strong>tter than measurement of serum cobalamin. (1) The deoxyuridine suppression test ( or “DUST”) has <strong>be</strong>en descri<strong>be</strong>d as a sensitive indicator of impaired thymidine synthesis due to either deficiency or metabolic inactivation of vitamin <strong>B12</strong> or folate.(58) However, DUST 32
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Why Vitamin B12 Deficiency Should be on your Radar Screen

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