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: 54.42). 01/2013; 368(2):149-60. DOI: 10.1056/NEJMcp1113996
Source: PubMed
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    ABSTRACT: Chemotherapy-related myelopathy mimicking subacute combined degeneration (SCD) has rarely been reported. We encountered a 35-year-old female with sensory ataxia after intrathecal chemotherapy. Spinal magnetic resonance imaging showed localized abnormal signal areas in the lateral and dorsal white matter, mimicking SCD. Diffusion imaging showed restricted water diffusion and increased microstructural complexity, and cerebrospinal fluid analysis showed increased levels of myelin basic proteins, indicating demyelinating myelopathy. Advanced diffusion imaging can provide more information on the microstructure of chemotherapy-related myelopathy.
    Case Reports in Neurology 05/2013; 5(2):110-5. DOI:10.1159/000351848
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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.
    Case Reports in Dermatology 05/2013; 5(2):186-91. DOI:10.1159/000353623
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    ABSTRACT: Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malabsorption and proteinuria comprising CUBN ligands were demonstrated by radiolabeled cobalamin uptake studies and SDS-PAGE, respectively. CUBN mRNA and protein expression were reduced ~10 fold and ~20 fold, respectively, in both ileum and kidney of affected dogs. DNA sequencing demonstrated a single base deletion in exon 53 predicting a translational frameshift and early termination codon likely triggering nonsense mediated mRNA decay. The mutant allele segregated with the disease in the border collie kindred. The border collie disorder indicates that a CUBN mutation far C-terminal from the intrinsic factor-cobalamin binding site can abrogate receptor expression and cause Imerslund-Gräsbeck syndrome.
    Molecular Genetics and Metabolism 05/2013; 109(4). DOI:10.1016/j.ymgme.2013.05.006 · 2.83 Impact Factor
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