| Literature DB >> 25390740 |
Peter M van Hasselt1, Sacha Ferdinandusse, Glen R Monroe, Jos P N Ruiter, Marjolein Turkenburg, Maartje J Geerlings, Karen Duran, Magdalena Harakalova, Bert van der Zwaag, Ardeshir A Monavari, Ilyas Okur, Mark J Sharrard, Maureen Cleary, Nuala O'Connell, Valerie Walker, M Estela Rubio-Gozalbo, Maaike C de Vries, Gepke Visser, Roderick H J Houwen, Jasper J van der Smagt, Nanda M Verhoeven-Duif, Ronald J A Wanders, Gijs van Haaften.
Abstract
Ketoacidosis is a potentially lethal condition caused by the imbalance between hepatic production and extrahepatic utilization of ketone bodies. We performed exome sequencing in a patient with recurrent, severe ketoacidosis and identified a homozygous frameshift mutation in the gene encoding monocarboxylate transporter 1 (SLC16A1, also called MCT1). Genetic analysis in 96 patients suspected of having ketolytic defects yielded seven additional inactivating mutations in MCT1, both homozygous and heterozygous. Mutational status was found to be correlated with ketoacidosis severity, MCT1 protein levels, and transport capacity. Thus, MCT1 deficiency is a novel cause of profound ketoacidosis; the present work suggests that MCT1-mediated ketone-body transport is needed to maintain acid-base balance.Entities:
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Year: 2014 PMID： 25390740 DOI： 10.1056/NEJMoa1407778
Source DB: PubMed Journal: N Engl J Med ISSN： 0028-4793 Impact factor: 91.245