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Research

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Featured article for January 2025
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This article from 2023 explores how genetic variations in the gene for the transcobalamin receptor (CD320) affect vitamin B12 uptake into the brain in elderly individuals. Vitamin B12 is vital for producing red blood cells, maintaining the nervous system, and other critical processes. The study found that certain gene variants are linked to higher levels of a specific form of B12 in the blood (holotranscobalamin or holo-TC), which might suggest altered cellular uptake.

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Key findings include:

  1. Gene Variants Detected: Four specific changes in the CD320 gene were found. About 12% of elderly individuals carry at least one of these variations.

  2. Impact on B12 Measurement: People with these variants had higher holo-TC levels. Holo-TC is a marker used to measure B12 availability in the body, but this study suggests it might not always reflect true B12 status.

  3. Clinical Implications: Since B12 status is often assessed using multiple markers like holo-TC, total B12, and methylmalonic acid, these findings suggest that genetic variations could lead to misleading test results in some individuals.

 

This study highlights the need to adjust current diagnostic tools for B12 deficiency to account for genetic variations in the CD320 gene. Without these adjustments, some individuals might be misdiagnosed as having normal B12 levels despite potential deficiency.

Featured article for December 2024

The article by Pluvinage et al (published in Sci. Transl. Med. 2024; 16:eadl3758) explores a novel autoimmune cause of vitamin B12 deficiency in the central nervous system (CNS), termed "Autoimmune B12 Central Deficiency" (ABCD). Researchers from San Francisco discovered autoantibodies targeting the transcobalamin receptor (CD320), a key protein in vitamin B12 transport, impairing B12 uptake into the brain despite normal serum B12 levels.
The authors have used phage display technology, and demonstrated the presence of a specific autoantibody against the CD320 receptor in a patient with poorly understood progressive neurological symptoms (e.g., tremor, ataxia, speech issues). It was observed that the autoantibody blocks B12 uptake into the brain, causing B12 deficiency in nervous tissue and leading to a variety of neurological symptoms. 
CD320 antibodies were also found in other patients with unexplained neurological deficits, neuropsychiatric lupus (21.4% prevalence), and some healthy controls (6% prevalence).
A genome-wide CRISPR screen revealed that an alternate pathway via LDL receptors compensates for CD320 loss in hematopoietic cells but not in the CNS, explaining the tissue-specific effects.
In the index patient, high-dose systemic vitamin B12 supplementation and immunosuppressive therapy showed improvements in CSF B12 levels and clinical symptoms. Larger studies are needed to explore the prevalence and long-term effects of these autoantibodies in people with symptoms suggestive of B12 deficiency, and the therapeutic role of B12 in neuropsychiatric disorders.

Link to our paper on B12 in plant-based diets
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Our paper on diagnostics and therapeutics of vitamin B12 deficiency, with emphasis on patient experiences, written on request of the BMJ Editorial Board

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Vitamin B12 Deficiency in Clinical Practice: Scientific Insights at the Bookends of Life-Proceedings of the First International B12 Conference, June 2023, Rotterdam'
The supplement consists of 88 pages and 14 peer-reviewed manuscripts published by the Food and Nutrition Bulletin 2024/ Supplement June 2024.

It can be found here:

https://journals.sagepub.com/toc/fnba/45/1_suppl

The congress organisers and authors hope that these publications will lead to a better understanding and knowledge of the complex spectrum of B12 deficiencies.

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cluB-12 - Registering for charitable status

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