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      How I treat cobalamin (vitamin B12) deficiency.

      Blood
      Disease Management, Humans, Malabsorption Syndromes, Practice Guidelines as Topic, Treatment Outcome, Vitamin B 12, metabolism, therapeutic use, Vitamin B 12 Deficiency, diagnosis, physiopathology, therapy

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          Abstract

          The challenges in medical management of cobalamin deficiency lie in attention to the unique pathophysiology that underlies cobalamin deficiency, more than in the mechanics of therapy. The central physiologic principles are that clinically important deficiency is more likely to occur (and progress) when intrinsic factor-driven absorption fails than when diet is poor and that most causes take years to produce clinically obvious deficiency. Transient defects have little clinical impact. The key management principle is the importance of follow-up, which also requires knowing how the deficiency arose. The virtues of these principles are not always fully appreciated. Recent developments have made diagnosis and management more difficult by diminishing the ability to determine cobalamin absorption status. Clinicians must also grapple with premature medicalization of isolated, mild biochemical changes that added many asymptomatic cases of still undetermined medical relevance to their caseload, often expanded by inflated cobalamin level criteria. The potential for misattribution of cobalamin-unrelated presentations to nongermane cobalamin and metabolite abnormalities has grown. Pathophysiologically based management requires systematic attention to each of its individual components: correctly diagnosing cobalamin deficiency, reversing it, defining its underlying cause, preventing relapse, managing the underlying disorder and its complications, and educating the patient.

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          Most cited references41

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          Vitamin B12, folic acid, and the nervous system.

          There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimer's disease and vascular dementia in elderly people.
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            Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies.

            Patients with cobalamin (vitamin B12) deficiency usually lack many of the classic features of severe megaloblastic anemia; because of the low diagnostic specificity of decreased serum cobalamin levels, demonstrating the deficiency unequivocally is often difficult. We examined the sensitivity of measuring serum concentrations of methylmalonic acid and total homocysteine for diagnosing patients with clear-cut cobalamin deficiency and compared the results with those of patients with clear-cut folate deficiency. Serum metabolites were measured for all patients seen from 1982 to 1989 at two university hospitals who met the criteria for cobalamin and folate deficiency states and for such patients seen from 1968 to 1981 from whom stored sera were available. In all, 406 patients had 434 episodes of cobalamin deficiency and 119 patients had 123 episodes of folate deficiency. Criteria for deficiency states included serum vitamin levels, hematologic and neurologic findings, and responses to therapy. Responses were documented in 97% of cobalamin-deficient patients and 76% of folate-deficient patients. Metabolite levels were measured by modified techniques using capillary-gas chromatography and mass spectrometry. Most of the cobalamin-deficient patients had underlying pernicious anemia; two thirds were blacks or Latinos. Hematocrits were normal in 28% and mean cell volumes in 17%. Of the 434 episodes of cobalamin deficiency, 98.4% of serum methylmalonic acid levels and 95.9% of serum homocysteine levels were elevated (greater than 3 standard deviations above the mean in normal subjects). Only one patient had normal levels of both metabolites. Serum homocysteine levels were increased in 91% of the 123 episodes of folate deficiency. Methylmalonic acid was elevated in 12.2% of the folate-deficient patients; in all but one, the elevation was attributable to renal insufficiency or hypovolemia. For the cobalamin-deficient patients, measuring serum metabolite concentrations proved to be a highly sensitive test of deficiency. We conclude that normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.
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              Prevalence of undiagnosed pernicious anemia in the elderly.

              R Carmel (1996)
              Existing information about the prevalence of pernicious anemia is largely based on older surveys that favored florid manifestations, tended to be retrospective analyses of previously diagnosed disease, and usually studied homogeneous European populations. The lack of current data in the United States has, among other things, hampered discussions of the proposal to increase folate intake by the general population. To estimate the prevalence of undiagnosed and untreated pernicious anemia among the elderly. A prospective survey of cobalamin levels and anti-intrinsic factor antibody was done in the elderly. Blood testing was done in 729 people aged 60 years or older and follow-up assessment with the Schilling test and other tests was offered when results were abnormal. Seventeen subjects were found to have pernicious anemia, usually with only minimal clinical manifestations of cobalamin deficiency. Although cobalamin deficiency had been suspected by the physicians of three subjects, they had been treated inadequately and still had evidence of deficiency. Excluding these three partially treated subjects from the analysis, 1.9% of the survey population had unrecognized and untreated pernicious anemia. The prevalence was 2.7% in women and 1.4% in men; 4.3% of the black women and 4.0% of the white women had pernicious anemia. Undiagnosed pernicious anemia is a common finding in the elderly, especially among black and white women. If these findings can be extrapolated, almost 800000 elderly people in the United States have undiagnosed and untreated pernicious anemia, and, thus, would be at possible risk for masked cobalamin deficiency if exposed to large amounts of folate. This number does not include those elderly with cobalamin deficiency caused by other disorders or the still unknown number of younger people with unrecognized pernicious anemia and other causes of deficiency.
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                Author and article information

                Journal
                18606874
                2532799
                10.1182/blood-2008-03-040253

                Chemistry
                Disease Management,Humans,Malabsorption Syndromes,Practice Guidelines as Topic,Treatment Outcome,Vitamin B 12,metabolism,therapeutic use,Vitamin B 12 Deficiency,diagnosis,physiopathology,therapy

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