title: Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damage.
abstract: BACKGROUND
  Congenital hyperinsulinism (CHI) is the most frequent cause of hypoglycemia in children. In addition to increased peripheral glucose utilization, dysregulated insulin secretion induces profound hypoglycemia and neuroglycopenia by inhibiting glycogenolysis, gluconeogenesis and lipolysis. This results in the shortage of all cerebral energy substrates (glucose, lactate and ketones), and can lead to severe neurological sequelae. Patients with CHI unresponsive to medical treatment can be subjected to near-total pancreatectomy with increased risk of secondary diabetes. Ketogenic diet (KD), by reproducing a fasting-like condition in which body fuel mainly derives from beta-oxidation, is intended to provide alternative cerebral substrates such ketone bodies. We took advantage of known protective effect of KD on neuronal damage associated with GLUT1 deficiency, a disorder of impaired glucose transport across the blood-brain barrier, and administered KD in a patient with drug-unresponsive CHI, with the aim of providing to neurons an energy source alternative to glucose.
  
  
  METHODS
  A child with drug-resistant, long-standing CHI caused by a spontaneous GCK activating mutation (p.Val455Met) suffered from epilepsy and showed neurodevelopmental abnormalities. After attempting various therapeutic regimes without success, near-total pancreatectomy was suggested to parents, who asked for other options. Therefore, we proposed KD in combination with insulin-suppressing drugs.
  
  
  RESULTS
  We administered KD for 2 years. Soon after the first six months, the patient was free of epileptic crises, presented normalization of EEG, and showed a marked recover in psychological development and quality of life.
  
  
  CONCLUSIONS
  KD could represent an effective treatment to support brain function in selected cases of CHI.
authors.affiliation: Metabolic Unit, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, piazza S. Onofrio 4, 00165, Rome, Italy. arianna.maiorana@opbg.net.
authors.forename: Arianna
authors.initials: A
authors.lastname: Maiorana
authors.affiliation: Metabolic Unit, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, piazza S. Onofrio 4, 00165, Rome, Italy. lucilla.manganozzi@hotmail.it.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Manganozzi
authors.affiliation: Department of Experimental Medicine, University of Tor Vergata and Bambino Gesù Children's Hospital, Rome, Italy. fabrizio.barbetti@uniroma2.it.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Barbetti
authors.affiliation: Clinical Nutrition, Gastroenterology Department, Bambino Gesù Children's Hospital, Rome, Italy. silviamaria.bernabei@opbg.net.
authors.forename: Silvia
authors.initials: S
authors.lastname: Bernabei
authors.affiliation: Metabolic Unit, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, piazza S. Onofrio 4, 00165, Rome, Italy. giorgia.gallo@opbg.net.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Gallo
authors.affiliation: Neurology, Neuroscience Department, Bambino Gesù Children's Hospital, Rome, Italy. raffaella.cusmai@opbg.net.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Cusmai
authors.affiliation: Psychology Unit, Neuroscience Department, Bambino Gesù Children's Hospital, Rome, Italy. stefania.caviglia@opbg.net.
authors.forename: Stefania
authors.initials: S
authors.lastname: Caviglia
authors.affiliation: Metabolic Unit, Department of Pediatric Medicine, Bambino Gesù Children's Hospital, piazza S. Onofrio 4, 00165, Rome, Italy. carlo.dionisivici@opbg.net.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dionisi-Vici
mesh_terms: D001930:Brain Injuries / Q000178:diet therapy* / Q000209:etiology / Q000517:prevention & control*; D002648:Child; D044903:Congenital Hyperinsulinism / Q000150:complications / Q000175:diagnosis* / Q000178:diet therapy*; D055423:Diet, Ketogenic / Q000379:methods*; D005260:Female; D006801:Humans; D016896:Treatment Outcome