Amnionless (AMN) mutations in Imerslund-Gräsbeck syndrome may be associated with disturbed vitamin B12 transport into the CNS

Journal of Inherited Metabolic Disease
A S LuderJ H Walter

Abstract

Familial selective vitamin B12 (cobalamin, Cbl) malabsorption (Imerslund-Gräsbeck syndrome, IGS, OMIM 261100) is a group of autosomal recessive disorders characterized by selective malabsorption of Cbl from the terminal ileum in the presence of normal histology. Mutations in the amnionless (AMN) and cubilin (CUBN) genes are known to be causes of IGS. Their gene products combine to form a receptor complex (cubam), which is instrumental in the binding and transport of Cbl in the gut. As opposed to Cbl transport in the terminal ileum, normal transport of Cbl into the CNS is poorly understood and little is known regarding its molecular basis. Studies in adults with neuropsychiatric disease have suggested the presence of an active transport mechanism into the central nervous system constituting a blood-brain barrier (BBB) for Cbl. A child with IGS, compound heterozygous for a missense and a nonsense mutation in the amnionless (AMN) protein gene, was noted to have a high daily cobalamin (Cbl) requirement for neuropsychiatric, but not for systemic metabolic and haematological, remission. Measurements of CSF Cbl revealed evidence that the transport of Cbl into the central nervous system was impaired, and a standard Schilling test was c...Continue Reading

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Citations

Nov 15, 2011·Orphanet Journal of Rare Diseases·Cameron M BeechStephan M Tanner
Nov 28, 2012·Clinical Chemistry and Laboratory Medicine : CCLM·Susanne H KirschRima Obeid
Oct 26, 2013·BMC Medical Genetics·Tina StormRenata Kozyraki
Jan 13, 2018·Diabetes, Obesity & Metabolism·Elizabeth G Mietlicki-BaaseMatthew R Hayes
Dec 13, 2018·Nature Communications·Casper LarsenChristian Brix Folsted Andersen
Feb 18, 2020·International journal for vitamin and nutrition research. Internationale Zeitschrift für Vitamin- und Ernährungsforschung. Journal international de vitaminologie et de nutrition·María S Jaureguiberry, Andrés Venturino
Jan 8, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Erik I ChristensenHenrik Birn
Jan 23, 2016·PloS One·Yiting ZhangRichard C Deth
Jun 1, 2019·Annual Review of Nutrition·Kendra A TianiMartha S Field
Jan 26, 2021·International Journal of Laboratory Hematology·Mohamed ElshinawyKhalid A Al-Thihli
Aug 8, 2021·British Journal of Pharmacology·Tito BornerBart C De Jonghe

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