title: Heterozygous Monocarboxylate Transporter 1 (MCT1, SLC16A1) Deficiency as a Cause of Recurrent Ketoacidosis.
abstract: We describe two half-siblings with monocarboxylate transporter 1 (MCT1, SLC16A1) deficiency, a defect on ketone body utilization, that has only recently been identified (van Hasselt et al., N Engl J Med, 371:1900-1907, 2014) as a cause for recurrent ketoacidoses. Our index patient is a boy with non-consanguineous parents who had presented acutely with impaired consciousness and severe metabolic ketoacidosis following a 3-day history of gastroenteritis at age 5 years. A 12.5-year-old half-brother who shared the proband's mother also had a previous history of recurrent ketoacidoses. Results of mutation and enzyme activity analyses in proband samples advocated against methylacetoacetyl-coenzyme A thiolase ("beta-ketothiolase") and succinyl-coenzyme A: 3-oxoacyl coenzyme A transferase (SCOT) deficiencies. A single heterozygous c.982C>T transition in the SLC16A1 gene resulting in a stop mutation (p.Arg328Ter) was detected in both boys. It was shared by their healthy mother and by the proband's half-sister, but was absent in the proband's father. MCT1 deficiency may be more prevalent than is apparent, as clinical manifestations can occur both in individuals with bi- and monoallelic mutations. It may be an important differential diagnosis in recurrent ketoacidosis with or without hypoglycemia, particularly in the absence of any specific metabolic profiles in blood and urine. Early diagnosis may enable improved disease management. Careful identification of potential triggers of metabolic decompensations in individuals even with single heterozygous mutations in the SLC16A1 gene is indicated.
authors.affiliation: Metabolic Unit, Department of Rheumatology and Metabolic Medicine, Princess Margaret Hospital, Perth, WA, Australia.|School of Paediatrics and Child Health, University of Western Australia, Perth, WA, Australia.
authors.forename: Shanti
authors.initials: S
authors.lastname: Balasubramaniam
authors.affiliation: PathWest Laboratories WA, Princess Margaret Hospital, Perth, WA, Australia.
authors.forename: Barry
authors.initials: B
authors.lastname: Lewis
authors.affiliation: PathWest Laboratories WA, Princess Margaret Hospital, Perth, WA, Australia.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Greed
authors.affiliation: Clinical Chemistry & Biochemistry, University Children's Hospital, Zürich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Meili
authors.affiliation: Clinical Chemistry & Biochemistry, University Children's Hospital, Zürich, Switzerland.
authors.forename: Annegret
authors.initials: A
authors.lastname: Flier
authors.affiliation: Medizinisches Versorgungszentrum, Dr Eberhard & Partner, Dortmund, Germany.
authors.forename: Raina
authors.initials: R
authors.lastname: Yamamoto
authors.affiliation: Clinical Institute of Laboratory Diagnostics, University Hospital Center Zagreb, Zagreb, Croatia.
authors.forename: Karmen
authors.initials: K
authors.lastname: Bilić
authors.affiliation: Bioanalytics & Biochemistry, Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359, Rheinbach, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Till
authors.affiliation: Bioanalytics & Biochemistry, Department of Natural Sciences, Bonn-Rhein-Sieg University of Applied Sciences, von-Liebig-Str. 20, 53359, Rheinbach, Germany. joern.oliver.sass@h-brs.de.
authors.forename: Jörn Oliver
authors.initials: JO
authors.lastname: Sass