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Lookup NU author(s): Dr Millie FullertonORCiD, Lauren Charlotte Phillips Phillips, Dr Rachael RedgraveORCiD, Dr Luke Spray, George MercesORCiD, Scott Kerridge, Professor Gavin RichardsonORCiD, Becky Crossley, Dr Simon BamforthORCiD, Dr Helen PhillipsORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The sodium-dependent multivitamin transporter, encoded by SLC5A6, mediates cellular uptake of biotin and pantothenic acid, essential cofactors for energy metabolism. We identified two families with SLC5A6 mutations presenting with early-onset dilated cardiomyopathy (DCM). To investigate the link between vitamin deficiency and cardiomyopathy, we generated a cardiac-specific SLC5A6 knockout (Slc5a6cKO) mouse model and evaluated the impact of vitamin supplementation. Slc5a6cKO mice developed progressive cardiac dysfunction, culminating in cardiac pathology and premature death at 26 weeks; earlier stages exhibited cardiomyocyte hypertrophy, fibrosis, impaired Coenzyme A synthesis, and metabolic imbalance, indicating progression toward cardiomyopathy. Cardiac magnetic resonance imaging and ECG confirmed progressive functional decline. Proteomic analysis revealed early mitochondrial metabolic disruption and extracellular matrix protein upregulation at 8 weeks, preceding overt cardiac dysfunction. Strikingly, vitamin supplementation from preconception onwards prevented the cardiac phenotype, preserving cardiac structure, function, morphology and survival. This paralleled the clinical outcome in one patient who received early vitamin treatment, compared to another who required a heart transplant without vitamin treatment. This study establishes a direct link between SLC5A6-mediated vitamin transport, mitochondrial function, and cardiac health. It highlights how vitamin deficiency contributes to cardiomyopathy pathogenesis and supports early vitamin supplementation as a potential therapeutic strategy for metabolic cardiomyopathies.
Author(s): Fullerton MO, Phillips LC, Redgrave RE, Spray L, Haufroid V, Merces G, Kerridge ST, Richardson GD, Mercier N, Roland D, Crossley R, Morgan ADH, Dewulf JP, Burn J, Bamforth SD, Phillips HM
Publication type: Article
Publication status: Published
Journal: JCI Insight
Year: 2026
Pages: epub ahead of print
Online publication date: 02/06/2026
Acceptance date: 21/05/2026
Date deposited: 03/06/2026
ISSN (electronic): 2379-3708
Publisher: American Society for Clinical Investigation
URL: https://doi.org/10.1172/jci.insight.200381
DOI: 10.1172/jci.insight.200381
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