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Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease

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Abstract

Vitamin B12 (cobalamin) is essential in animals and humans for metabolism of methylmalonic acid, for the remethylation of homocysteine to methionine and, consequently, for all S-adenosylmethionine-dependent methylation reactions, including DNA synthesis. In man, cobalamin deficiency leads to anemia and neurologic and cognitive impairment. In the cblF inborn error of vitamin B12 metabolism, free vitamin accumulates in lysosomes and cannot be converted to cofactors for mitochondrial methylmalonyl-CoA mutase and cytosolic methionine synthase. Recent work has shown that this defect is caused by mutations in the lysosomal membrane protein LMBD1, which shows significant homology to lipocalin membrane receptors, thereby indicating that LMBD1 is a lysosomal membrane exporter for cobalamin.

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Acknowledgments

F.R. is supported by funds from “Innovative Medical Research” of University of Münster Medical School and the Interdisciplinary Center for Clinical Research, Münster, Germany. B.F. is supported by Swiss National Foundation grant number 320000_122568/1. The authors thank the parents and their children for participation in the study.

Conflict of interest statement

The authors reported no conflict of interests.

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Authors and Affiliations

  1. Department of General Pediatrics, Münster University Children’s Hospital, Münster, Germany

    Susann Gailus & Frank Rutsch

  2. Department of Biochemistry, Charité University Medical Center, Berlin, Germany

    Wolfgang Höhne

  3. Institut de Biologie Physico-Chimique, Centre National de la Recherche Scientifique, Université Paris Descartes, Paris, France

    Bruno Gasnier

  4. Cologne Center for Genomics, Institute for Human Genetics, University of Cologne, Cologne, Germany

    Peter Nürnberg

  5. Metabolic Unit, University Children’s Hospital, Basel, Switzerland

    Brian Fowler

  6. Klinik und Poliklinik für Kinder- und Jugendmedizin, Universitätsklinikum Münster, Albert-Schweitzer Strasse 33, 48149, Münster, Germany

    Frank Rutsch

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  1. Susann Gailus
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  2. Wolfgang Höhne
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  3. Bruno Gasnier
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  4. Peter Nürnberg
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  5. Brian Fowler
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  6. Frank Rutsch
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Correspondence to Frank Rutsch.

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Gailus, S., Höhne, W., Gasnier, B. et al. Insights into lysosomal cobalamin trafficking: lessons learned from cblF disease. J Mol Med 88, 459–466 (2010). https://doi.org/10.1007/s00109-010-0601-x

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  • DOI: https://doi.org/10.1007/s00109-010-0601-x

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