Continuous Glucose Monitoring Facilitates Diazoxide Use in the Management of Glut1 Deficiency Syndrome

Abstract Background: Glut1 deficiency syndrome (Glut1DS) is caused by mutations in SLC2A1 on chromosome 1p34.2, which impairs transmembrane glucose transport across the blood brain barrier resulting hypoglycorrhachia and decreased availability for metabolism. This causes a drug-resistant, metabolic epilepsy due to energy deficiency. Standard treatment Glut1DS ketogenic diet (KD) but options are limited if patients fail KD. Diazoxide, inhibits insulin release, was used sparingly past few increase levels thus intracerebral levels. Unfortunately, their complicated unacceptable persistent hyperglycemia with glucoses 300s 500s. We investigated use of continuous monitor (CGM) enable titration diazoxide therapy patient KD-resistant Glut1DS. Clinical Case: A 14-year-old girl (c.398_399delGCinsTT:p.Lys133Phe) failed KD severe nausea, vomiting, abdominal pain, hypertriglyceridemia. Laboratory tests revealed CSF 36 mg/dL when 93 mg/dL. Over course 3 hospitalizations targeting range 120-180 diazoxide, EEG seizure activity from 0 absence seizures per hour. CGM placement during third hospitalization showed an average interstitial 157 variability 20.8% dose 7.3 mg/kg/day. After discharge, has been adjust doses 2-4 times week achieve target 140-180 Repeat laboratory 55 158 Current 7.9 mg/kg/day most recent hemoglobin A1c 5.4%. Conclusions: first report demonstrating as tool facilitating safe initiation real-time who have Diazoxide addresses neuroglycopenia more physiologically raising subsequently allows accurate while avoiding complications introduces possibility becoming standard care More broadly, provides valuable management other disorders carbohydrate