Clinical spectrum and diagnosis of cobalamin deficiency [see comments]

Abstract

To better estimate how frequently patients with low serum cobalamin (Cbl) levels in current clinical practice are truly deficient in Cbl and to determine the incidence of atypical or nonclassic presentations of Cbl deficiency, we prospectively studied 300 unselected consecutive patients with serum Cbl concentrations less than 200 pg/mL seen at two medical centers over a 2-year period. Baseline hematologic, neuropsychiatric, and biochemical measurements were obtained, followed by a course of parenteral Cbl therapy and reassessment. A response to Cbl therapy was defined as one or more of the following: (1) an increase in hematocrit of 0.05 or more; (2) a decrease in mean cell volume of 5 fL or more; (3) a clearing of hypersegmented neutrophilis and macroovalocytes from the peripheral blood smear; and (4) an unequivocal and prompt improvement of neuropsychiatric abnormalities. Of the 300 patients with serum Cbl levels less than 200 pg/mL, 86 had one or more responses to Cbl therapy and 59 had no response. In 155, insufficient data was available. In the Cbl-responsive patients, normal values were found for the following tests: hematocrit, 44%; mean cell volume less than or equal to 100 fL, 36%; white blood cell count, 84%; platelet count, 79%; serum lactic dehydrogenase, 43%; and serum bilirubin, 83%. Peripheral blood smears were nondiagnostic in 6% when reviewed by the investigators, but 33% as reported by routine laboratories. Serum Cbl levels in the 100 to 199 pg/mL range were present in 38%. Neuropsychiatric abnormalities were noted in 28%, often in the absence of anemia, macrocytosis, or both. Serum levels of methylmalonic acid and/or total homocysteine were elevated greater than 3 SDs above the mean for normal subjects in 94% of the Cbl-responsive patients. We conclude that Cbl deficiency should be considered and investigated in patients with unexplained hematologic or neuropsychiatric abnormalities of the kind seen in Cbl deficiency, even if anemia, an elevated mean cell volume, a marked depression of the serum Cbl, or other classic hematologic or biochemical abnormalities are lacking. Levels of serum methylmalonic acid and total homocysteine are useful as ancillary diagnostic tests in the diagnostis of Cbl deficiency.

Potential outcome factors in subacute combined degeneration

“…While the majority of patients in our study had pernicious anemia, our findings suggest that the absence of anemia was associated with higher rates of resolution of neurologic deficits after B12 therapy. This finding was surprising as the severity of hematological changes in subjects with pernicious anemia does not appear to correlate with neurological complications 2,60 . Also, among the factors analyzed, laboratory markers of pernicious anemia had weaker associations with resolution of signs and symptoms.…”

“…While several medical specialties are likely to evaluate patients with subacute combined degeneration, little information on predictors of outcome is available 1,2,60–62 . In this investigation, we used published data to generate hypotheses regarding potential correlates of outcomes and found that clinical, laboratory, and MRI findings at the time of diagnosis may correlate with complete resolution of signs and symptoms in subacute combined degeneration.…”

“…Vitamin B12 deficiency can lead to serious neurologic complications including peripheral neuropathy, bilateral cerebral dysfunction, optic neuropathy, memory loss, personality changes, impaired recall, and subacute combined degeneration of the spinal cord 1,2 . Subacute combined degeneration is a rapidly progressive myelopathy that can be associated with profound neurologic deficits including progressive sensory abnormalities, ascending paresthesias, weakness, ataxia, loss of sphincter control, and gait impairment 1–7 . In some patients with vitamin B12 deficiency, subacute combined degeneration can be triggered by brief exposure to nitrous oxide during anesthesia 8–10 and in others after prolonged recreational use of the drug 11 .…”

Severe vitamin B12 deficiency resulting in pancytopenia, splenomegaly and leukoerythroblastosis

“…Although B12 levels may not be entirely reliable, levels above 300 ng/L are generally considered to exclude significant B12 deficiency while levels less than 150 ng/L are felt to be consistent with B12 deficiency and therefore the MMA assay is not needed under those circumstances (8). It should be kept in mind that not all patients with B12 deficiency are anemic and not all patients have elevated MCV (2, 11, 12).…”

Cellular folate vitamer distribution during and after correction of vitamin B12 deficiency: a case for the methylfolate trap

“…The population prevalence of vitamin B 12 deficiency is high, particularly among elderly people, where reported prevalence range from 12% to 40% in selected groups (Andres et al , 2004). Vitamin B 12 deficiency has a number of sequellae, including hyperhomocysteinaemia, neuropathy, megaloblastic anaemia and deterioration of cognitive function (Stabler et al , 1990).…”