Exercise-induced lactic acidemia associated with a SLC16A13 biallelic variant

The molecular basis of impaired lactate clearance and exercise-induced lactic acidemia remains largely unknown. Here, we report a 10-year-old Thai girl, born to consanguineous parents, with growth delay and partial growth hormone deficiency. The proband underwent detailed clinical phenotyping, exercise stress testing, metabolic profiling, and genome sequencing. She presented with profound exercise-induced lactic acidemia, characterized by elevated blood lactate (3.7-fold above baseline) and severely compromised clearance. Genome sequencing identified a novel homozygous frameshift variant in the solute carrier gene SLC16A13 (c.24delC, p.Asp9Thrfs*50). To assess causality, Slc16a13 knockout mice were generated and subjected to treadmill exercise and biochemical assays, revealing impaired decline of blood lactate after exercise (p = 0.001) and altered amino acid metabolism. These findings implicate SLC16A13 as a critical regulator of lactate metabolism in humans and establish a direct link between biallelic SLC16A13 variants and exercise-induced lactic acidemia, highlighting a novel genetic mechanism underlying exercise stress and metabolic dysregulation.