Here, we report for the first time female monozygotic twins with PDC-E1α deficiency, caused by a novel missense mutation in exon 11 of PDHA1. Both twins presented with a similar, primarily neurological phenotype but showed clear differences in disease severity, residual PDC activities, and XCI ratios in blood. This evidence concerns the gene PDC and hyperinsulinemic hypoglycemia, familial, 4.