A SLC16A1 Mutation in an Infant With Ketoacidosis and Neuroimaging Assessment: Expanding the Clinical Spectrum of MCT1 Deficiency

Frontiers in Pediatrics
Sara Al-KhawagaKhalid Hussain

Abstract

The solute carrier family 16 member 1 (SLC16A1) gene encodes for monocarboxylate transporter 1 (MCT1) that mediates the movement of monocarboxylates, such as lactate and pyruvate across cell membranes. Inactivating recessive homozygous or heterozygous mutations in the SLC16A1 gene were described in patients with recurrent ketoacidosis and hypoglycemia, a potentially lethal condition. In the brain where MCT1 is highly localized around axons and oligodendrocytes, glucose is the most crucial energy substrate while lactate is an alternative substrate. MCT1 mutation or reduced expression leads to neuronal loss due to axonal degeneration in an animal model. Herein, we describe a 28 months old female patient who presented with the first hypoglycemic attack associated with ketoacidosis starting at the age of 3 days old. Whole exome sequencing (WES) performed at 6 months of age revealed a c.218delG mutation in exon 3 in the SLC16A1 gene. The variant is expected to result in loss of normal MCT1 function. Our patient is amongst the youngest presenting with MCT1 deficiency. A detailed neuroimaging assessment performed at 18 months of age revealed a complex white and gray matter disease, with heterotopia. The threshold of blood glucose to c...Continue Reading

References

Dec 11, 1971·Lancet·R S DaumC R Scriver
Mar 1, 1972·The Journal of Clinical Investigation·J T Tildon, M Cornblath
Jan 15, 2000·Diabetes/metabolism Research and Reviews·L Laffel
Apr 15, 2000·Nature·M W SchwartzD G Baskin
Nov 6, 2003·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ching-Ping Chih, Eugene L Roberts
May 8, 2004·The Journal of Physiology·L B Gladden
Jul 9, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tonya M BlissRobert M Sapolsky
Aug 6, 2005·Science·Tony K T LamLuciano Rossetti
Dec 3, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Denis BurdakovAlexei Verkhratsky
Jan 13, 2006·Brain Research·Oriana ChiryStéphanie Clarke
Mar 6, 2008·The Journal of Clinical Endocrinology and Metabolism·Paul E SijensRoelineke J Lunsing
Apr 12, 2011·Journal of Inherited Metabolic Disease·Jörn Oliver Sass
Aug 23, 2011·Neurobiology of Disease·Fredrik LauritzenTore Eid
May 25, 2012·Nature·Ursula FünfschillingKlaus-Armin Nave
Jul 18, 2012·Nature·Youngjin LeeJeffrey D Rothstein
Mar 20, 2013·Molecular Aspects of Medicine·Andrew P Halestrap
Aug 31, 2013·Trends in Cell Biology·Brett M MorrisonJeffrey D Rothstein
Jan 11, 2014·Clinical and Translational Imaging : Reviews in Nuclear Medicine and Molecular Imaging·Lisa Mosconi
Nov 13, 2014·The New England Journal of Medicine·Peter M van HasseltGijs van Haaften
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Mar 20, 2016·Biochimica Et Biophysica Acta·Jhudit Pérez-EscuredoPierre Sonveaux
Sep 30, 2016·Scientific Reports·Roberto Elizondo-VegaMaría de Los Angeles García-Robles
Mar 4, 2017·Therapeutic Advances in Psychopharmacology·Laurel RiskeSerdar M Dursun
Apr 24, 2018·Journal of Applied Genetics·Abramowicz Anna, Gos Monika

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Citations

Apr 23, 2020·Neuroradiology·Manal Nicolas-JilwanMoeenaldeen AlSayed

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Methods Mentioned

BETA
Exome Sequencing

Software Mentioned

Applied Biosystems Sequencing Analysis
Applied Biosystems SeqScape

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