TY - JOUR
T1 - Monocarboxylate Transporter 1 Deficiency and Ketone Utilization
AU - van Hasselt, Peter M.
AU - Ferdinandusse, Sacha
AU - Monroe, Glen R.
AU - Ruiter, Jos P. N.
AU - Turkenburg, Marjolein
AU - Geerlings, Maartje J.
AU - Duran, Karen
AU - Harakalova, Magdalena
AU - van der Zwaag, Bert
AU - Monavari, Ardeshir A.
AU - Okur, Ilyas
AU - Sharrard, Mark J.
AU - Cleary, Maureen
AU - O'Connell, Nuala
AU - Walker, Valerie
AU - Rubio-Gozalbo, M. Estela
AU - de Vries, Maaike C.
AU - Visser, Gepke
AU - Houwen, Roderick H. J.
AU - van der Smagt, Jasper J.
AU - Verhoeven-Duif, Nanda M.
AU - Wanders, Ronald J. A.
AU - van Haaften, Gijs
PY - 2014/11/13
Y1 - 2014/11/13
N2 - 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.
AB - 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.
U2 - 10.1056/NEJMoa1407778
DO - 10.1056/NEJMoa1407778
M3 - Article
C2 - 25390740
SN - 0028-4793
VL - 371
SP - 1900
EP - 1907
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 20
ER -