Monocarboxylate Transporter 1 Deficiency and Ketone Utilization


Creative Commons License

van Hasselt P. M. , Ferdinandusse S., Monroe G. R. , Ruiter J. P. N. , Turkenburg M., Geerlings M. J. , ...Daha Fazla

NEW ENGLAND JOURNAL OF MEDICINE, cilt.371, sa.20, ss.1900-1907, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 371 Konu: 20
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1056/nejmoa1407778
  • Dergi Adı: NEW ENGLAND JOURNAL OF MEDICINE
  • Sayfa Sayıları: ss.1900-1907

Özet

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.