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.

Appendices

One-Sentence Take-Home Message

MCT1 deficiency is an only recently described cause of recurrent ketoacidosis with clinical manifestation observed both in individuals with bi- or monoallelic mutations.

Compliance with Ethics Guidelines

Conflict of Interest

Shanti Balasubramaniam, Barry Lewis, Lawrence Greed, David Meili, Annegret Flier, Raina Yamamoto, Karmen Bilić, Claudia Till, and Jörn Oliver Sass declare have no conflict of interest.

Informed Consent and Animal Rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000.

The investigated family has agreed to the publication and provided informed consent. This article does not contain any studies with animal subjects performed by the any of the authors.

Details of the Contributions of Individual Authors

SB was the physician in charge of the family. BL, LG, DM, AF, RY, KB, CT, and JOS performed/supervised/interpreted laboratory investigations. SB and JOS have drafted the manuscript. All authors have read/critically revised the manuscript.