ESPE Abstracts

Background: Recurrent episodes of ketoacidosis with or without hypoglycemia have been reported with homozygous or heterozygous mutations in the solute carrier family 16 member 1 (SLC16A1) gene. This gene encodes for the monocarboxylate transporter 1 (MCT-1) which plays a key role in lactate, pyruvate and ketone body transport.

Objective(s): To describe the youngest patient with a novel SLC16A1 gene who presented with recurrent episodes of ketoacidosis and hypoglycemia.

Case presentation: The patient was born following a NVD. At 3 days of age she presented with hypothermia and acidosis. At 6 months, she presented again with vomiting and was biochemically noticed to have hypoglycemia and metabolic acidosis. Family history was significant for consanguinity (first degree cousin parents). Our patient is developmentally normal at the age of 2.

Methods: Whole Exome Sequencing (WES) analysis was performed in the patient at 6 months of age and her parents using NetGen sequencing on an Illumina system. Sequence and copy number alterations were reported according to the Human Genome Variation Society (HGVS) and International System for human Cytogenetic Nomenclature (ISCN) guideline.

Results: WES showed that the patient was homozygous for the c.218delG pathogenic mutation in the SLC16A1 Gene (P.Gly73ValfsX8 in exon 3 in the SLC16A1 gene). The patient’s mother and father were heterozygous for the mutation. The c.218delG mutation has not been reported previously as a pathogenic or benign. The c.218delG mutation causes a frameshift starting with codon Glycine 73, changing this amino acid to Valine residue and creating a premature Stop codon at position 8 of the new reading frame. This identified mutation is anticipated to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.218delG mutation is not observed in large population cohorts.

Conclusions: We report a novel mutation in the SLC16A1 gene leading to recurrent metabolic ketoacidosis and hypoglycemia. Our patient is one of the youngest presenting and diagnosed with this disorder. Further research is required to understand the role of the MCT-1 in key tissues such as the liver, muscle and ketone body metabolism. Disruption of MCT1 in the central nervous system produces axon damage and neuronal loss in mice, yet it remains unclear at this stage whether this is a direct effect of the absence of MCT1 in the brain or caused by episodes of profound ketoacidosis. Nevertheless, neurodevelopmental follow up should be considered in this patient.