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In Reply: We thank Dr. Phillips for his inquiry.
In general, serum vitamin B12 concentrations vary greatly, and we acknowledge that serum vitamin B12 may be normal in up to 5% of patients with documented B12 deficiency.1 In a prospective study of 1,599 patients, Matchar et al2 demonstrated that a single vitamin B12 level less than 200 pg/mL had a specificity greater than 95% at predicting vitamin B12 deficiency.2 We acknowledge that additional metabolite testing is necessary in equivocal cases in which the vitamin B12 level is between 200 and 300 pg/mL, which is often considered to be the normal range, but the patient has symptoms of vitamin B12 deficiency such as dementia and unexplained macrocytosis, and neurologic symptoms.3
Based on the patient’s symptoms of neuropathy and fatigue in conjunction with a vitamin B12 level well below 200 pg/mL, we believe that the diagnosis can be made.2,3 Nonetheless, although we did not mention it in our article, we did indeed send for a methylmalonic acid measurement at the time of the initial evaluation, and the level was elevated at 396 nmol/L (normal 87–318 nmol/L), further confirming her vitamin B12 deficiency.
- Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995; 346:85–89.
- Matchar DB, McCrory DC, Millington DS, Feussner JR. Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency. Am J Med Sci 1994; 308:276–283.
- Stabler SP. Clinical practice. Vitamin B12 deficiency. N Eng J Med 2013; 368:149–160.
In Reply: We thank Dr. Phillips for his inquiry.
In general, serum vitamin B12 concentrations vary greatly, and we acknowledge that serum vitamin B12 may be normal in up to 5% of patients with documented B12 deficiency.1 In a prospective study of 1,599 patients, Matchar et al2 demonstrated that a single vitamin B12 level less than 200 pg/mL had a specificity greater than 95% at predicting vitamin B12 deficiency.2 We acknowledge that additional metabolite testing is necessary in equivocal cases in which the vitamin B12 level is between 200 and 300 pg/mL, which is often considered to be the normal range, but the patient has symptoms of vitamin B12 deficiency such as dementia and unexplained macrocytosis, and neurologic symptoms.3
Based on the patient’s symptoms of neuropathy and fatigue in conjunction with a vitamin B12 level well below 200 pg/mL, we believe that the diagnosis can be made.2,3 Nonetheless, although we did not mention it in our article, we did indeed send for a methylmalonic acid measurement at the time of the initial evaluation, and the level was elevated at 396 nmol/L (normal 87–318 nmol/L), further confirming her vitamin B12 deficiency.
In Reply: We thank Dr. Phillips for his inquiry.
In general, serum vitamin B12 concentrations vary greatly, and we acknowledge that serum vitamin B12 may be normal in up to 5% of patients with documented B12 deficiency.1 In a prospective study of 1,599 patients, Matchar et al2 demonstrated that a single vitamin B12 level less than 200 pg/mL had a specificity greater than 95% at predicting vitamin B12 deficiency.2 We acknowledge that additional metabolite testing is necessary in equivocal cases in which the vitamin B12 level is between 200 and 300 pg/mL, which is often considered to be the normal range, but the patient has symptoms of vitamin B12 deficiency such as dementia and unexplained macrocytosis, and neurologic symptoms.3
Based on the patient’s symptoms of neuropathy and fatigue in conjunction with a vitamin B12 level well below 200 pg/mL, we believe that the diagnosis can be made.2,3 Nonetheless, although we did not mention it in our article, we did indeed send for a methylmalonic acid measurement at the time of the initial evaluation, and the level was elevated at 396 nmol/L (normal 87–318 nmol/L), further confirming her vitamin B12 deficiency.
- Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995; 346:85–89.
- Matchar DB, McCrory DC, Millington DS, Feussner JR. Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency. Am J Med Sci 1994; 308:276–283.
- Stabler SP. Clinical practice. Vitamin B12 deficiency. N Eng J Med 2013; 368:149–160.
- Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J. Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations. Lancet 1995; 346:85–89.
- Matchar DB, McCrory DC, Millington DS, Feussner JR. Performance of the serum cobalamin assay for diagnosis of cobalamin deficiency. Am J Med Sci 1994; 308:276–283.
- Stabler SP. Clinical practice. Vitamin B12 deficiency. N Eng J Med 2013; 368:149–160.