Article

Clinical practice. Vitamin B12 deficiency

Division of Hematology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
New England Journal of Medicine (Impact Factor: 55.87). 01/2013; 368(2):149-60. DOI: 10.1056/NEJMcp1113996
Source: PubMed
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    • "While factors responsible for vitamin B 12 entry into brain have not been fully elucidated, cubilin and megalin, which combine to participate in transport of vitamin B 12 in other tissues, are expressed in the choroid plexus[14,15], and a role for amnionless has been postulated based upon disturbed vitamin B 12 transport into the brain in a patient with a mutation causing Imerslund-Gräsbeck syndrome[16]. While diet or genetic defects in transport/ processing can affect systemic vitamin B 12 availability[17,18], there have been relatively few direct studies of vitamin B 12 status in human brain[19,20]and none have provided a comprehensive analysis of different Cbl species. Methylation of DNA and histone proteins complexly regulates gene expression and this form of epigenetic regulation is particularly important during development, including pre-and postnatal brain development[21]. "
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    ABSTRACT: Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "The diagnosis of vitamin B12 deficiency can be done with initial testing of vitamin B12 assay [1]. Extremely low level (<100 pg per milliliter) is usually associated with clinical deficiency [1]. "
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    ABSTRACT: A 52-year-old male with no significant past medical history reports increasing generalized fatigue and weakness for the past 2 weeks. Physical examination reveals jaundice and pallor without organomegaly or lymphadenopathy. His hemoglobin was 5.9 g/dL with a mean corpuscular volume of 87.1 fL and elevated red blood cell distribution width of 30.7%. His liver function test was normal except for elevated total bilirubin of 3.7 mg/dL. Serum LDH was 701 IU/L, and serum haptoglobin was undetectable. Further investigation revealed serum vitamin B12 of <30 pg/mL with elevated methylmalonic acid and homocysteine level. In addition, serum ferritin and transferrin saturation were low. The patient was diagnosed with hemolytic anemia secondary to vitamin B12 deficiency with concomitant iron deficiency anemia.
    Full-text · Article · Sep 2013
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    • "The treatment of N2O abuse-induced vitamin B12 deficiency is similar to the treatment of pernicious anemia, and comprises 1 of 2 regimens: (1) intramuscular injections of 1,000 µg vitamin B12 (cyanocobalamin) daily for 1 week, followed by weekly injections for 4–8 weeks, and then monthly injections until clinical resolution; or (2) daily oral administration of 1,000–2,000 µg cyanocobalamin until clinical resolution [15]. "
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    ABSTRACT: Vitamin B12 deficiency causes skin hyperpigmentation, subacute combined degeneration of the spinal cord, and megaloblastic anemia. Although vitamin B12 deficiency rarely occurs in well-nourished, healthy, young people, nitrous oxide (N2O) intoxication is an important cause of vitamin B12 deficiency in this cohort. N2O, a colorless gas used as an anesthetic since the late 19th century because of its euphoric and analgesic qualities, is now used as a recreational drug and is available via the Internet and at clubs. Here, we describe the case of a 29-year-old woman presenting with skin hyperpigmentation as her only initial symptom after N2O abuse for approximately 2 years. N2O intoxication-induced vitamin B12 deficiency was diagnosed based on the skin pigmentation that had manifested over the dorsa of her fingers, toes, and trunk, coupled with myeloneuropathy of the posterior and lateral columns, a low serum vitamin B12 level, an elevated serum homocysteine level, and the N2O exposure revealed while establishing the patient's history. Symptoms improved significantly with vitamin B12 treatment. We recommend that dermatologists consider N2O intoxication-induced vitamin B12 deficiency as a potential cause of skin hyperpigmentation and myeloneuropathy of the posterior and lateral columns in young, otherwise healthy patients. Failure to recognize this presentation may result in inappropriate treatment, thus affecting patients' clinical outcomes.
    Full-text · Article · May 2013 · Case Reports in Dermatology
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