Lumbar puncture has always represented the initial diagnostic step since the first descriptions of GLUT1 deficiency even if the increasing potentials of ultra-fast next-generation sequencing techniques, the recent validation of a less invasive blood test (e.g., METAGLUT1), and the detection of novel candidate cerebrospinal biomarkers (e.g., gluconic + galactonic acid, xylose-α1-3-glucose, and xylose-α1-3-xylose-α1-3-glucose) provided possible alternative diagnostic tools [4, 5]. The gene discussed is SLC2A1; the disease is hyperinsulinemic hypoglycemia, familial, 4.