Monocarboxylate Transporter 1 Deficiency and Ketone Utilization

Peter M. van Hasselt*, 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 SmagtNanda M. Verhoeven-Duif, Ronald J. A. Wanders, Gijs van Haaften

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.
Original languageEnglish
Pages (from-to)1900-1907
JournalNew England Journal of Medicine
Volume371
Issue number20
DOIs
Publication statusPublished - 13 Nov 2014

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