Ketogenic diet in a patient with congenital hyperinsulinism: a novel approach to prevent brain damageReport as inadecuate

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Orphanet Journal of Rare Diseases

, 10:120

First Online: 24 September 2015Received: 23 June 2015Accepted: 10 September 2015DOI: 10.1186-s13023-015-0342-6

Cite this article as: Maiorana, A., Manganozzi, L., Barbetti, F. et al. Orphanet J Rare Dis 2015 10: 120. doi:10.1186-s13023-015-0342-6


BackgroundCongenital 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.

MethodsA 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.

ResultsWe 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.

ConclusionsKD could represent an effective treatment to support brain function in selected cases of CHI.

KeywordsCongenital hyperinsulinism Ketogenic diet Hypoglycemia Epilepsy Neurodevelopment AbbreviationsCHICongenital hyperinsulinism

KDKetogenic diet


GLUT1Glucose transporter 1


FFAFree fatty acids

ROSRadical oxygen species

CNSCentral nervous system

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Author: Arianna Maiorana - Lucilla Manganozzi - Fabrizio Barbetti - Silvia Bernabei - Giorgia Gallo - Raffaella Cusmai - Stefania C


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