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Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations
BACKGROUND: Hyperinsulinemic hypoglycemia (HI) is the most frequent cause of recurrent hypoglycemia in children. Despite diagnostic and therapeutic advances, it remains an important cause of morbidity, leading to neurological complications, such as psychomotor retardation and epilepsy. Patients with...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507241/ https://www.ncbi.nlm.nih.gov/pubmed/34635134 http://dx.doi.org/10.1186/s13023-021-02045-3 |
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author | Maiorana, Arianna Caviglia, Stefania Greco, Benedetta Alfieri, Paolo Cumbo, Francesca Campana, Carmen Bernabei, Silvia Maria Cusmai, Raffaella Mosca, Antonella Dionisi-Vici, Carlo |
author_facet | Maiorana, Arianna Caviglia, Stefania Greco, Benedetta Alfieri, Paolo Cumbo, Francesca Campana, Carmen Bernabei, Silvia Maria Cusmai, Raffaella Mosca, Antonella Dionisi-Vici, Carlo |
author_sort | Maiorana, Arianna |
collection | PubMed |
description | BACKGROUND: Hyperinsulinemic hypoglycemia (HI) is the most frequent cause of recurrent hypoglycemia in children. Despite diagnostic and therapeutic advances, it remains an important cause of morbidity, leading to neurological complications, such as psychomotor retardation and epilepsy. Patients with diffuse drug-unresponsive HI manifest neurological impairment and neurobehavioral problems, even though surgically treated with a near-total pancreatectomy. Based on the analogies between HI and GLUT1 deficiency, both presenting with neuroglycopenia and lack of alternative cerebral energy sources, we administered a ketogenic diet (KD) in three drug-unresponsive GCK-HI patients with the aim of preserving neurodevelopment and avoiding the need of a near-total pancreatectomy. They presented recurrent symptomatic hypoglycemia, intellectual disability and refractory epilepsy. Patients were treated with classical KD for 79, 27 and 18 months, respectively. RESULTS: All patients became asymptomatic in a few days and showed an important improvement of the alert state. Epilepsy disappeared and no appearance of novel hypoglycemic lesions was detected with a brain MRI. Cognitive and adaptive abilities rapidly improved and normalized. IQ rose significantly from 81 to 111 (p = 0.04) in patient 1, from 82 vs 95 (p = 0.04) in patient 2, from 60 to 90 (p = 0.04) in patient 3. CONCLUSIONS: We demonstrated the safety and efficacy of KD in the treatment of drug-unresponsive GCK-HI at a short and long-term. The neuroprotective effects of KD determined the recovery from epilepsy and intellectual disabilities and averted the need of a near-total pancreatectomy. All patients and their families reported an improvement of physical and psychosocial well-being, with a substantial improvement of their quality of life. These results might change the course and the quality of life of these patients and their families, having a relevant impact on human lives. Therefore, KD might be considered the elective treatment in unresponsive forms of GCK-HI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-02045-3. |
format | Online Article Text |
id | pubmed-8507241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85072412021-10-20 Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations Maiorana, Arianna Caviglia, Stefania Greco, Benedetta Alfieri, Paolo Cumbo, Francesca Campana, Carmen Bernabei, Silvia Maria Cusmai, Raffaella Mosca, Antonella Dionisi-Vici, Carlo Orphanet J Rare Dis Research BACKGROUND: Hyperinsulinemic hypoglycemia (HI) is the most frequent cause of recurrent hypoglycemia in children. Despite diagnostic and therapeutic advances, it remains an important cause of morbidity, leading to neurological complications, such as psychomotor retardation and epilepsy. Patients with diffuse drug-unresponsive HI manifest neurological impairment and neurobehavioral problems, even though surgically treated with a near-total pancreatectomy. Based on the analogies between HI and GLUT1 deficiency, both presenting with neuroglycopenia and lack of alternative cerebral energy sources, we administered a ketogenic diet (KD) in three drug-unresponsive GCK-HI patients with the aim of preserving neurodevelopment and avoiding the need of a near-total pancreatectomy. They presented recurrent symptomatic hypoglycemia, intellectual disability and refractory epilepsy. Patients were treated with classical KD for 79, 27 and 18 months, respectively. RESULTS: All patients became asymptomatic in a few days and showed an important improvement of the alert state. Epilepsy disappeared and no appearance of novel hypoglycemic lesions was detected with a brain MRI. Cognitive and adaptive abilities rapidly improved and normalized. IQ rose significantly from 81 to 111 (p = 0.04) in patient 1, from 82 vs 95 (p = 0.04) in patient 2, from 60 to 90 (p = 0.04) in patient 3. CONCLUSIONS: We demonstrated the safety and efficacy of KD in the treatment of drug-unresponsive GCK-HI at a short and long-term. The neuroprotective effects of KD determined the recovery from epilepsy and intellectual disabilities and averted the need of a near-total pancreatectomy. All patients and their families reported an improvement of physical and psychosocial well-being, with a substantial improvement of their quality of life. These results might change the course and the quality of life of these patients and their families, having a relevant impact on human lives. Therefore, KD might be considered the elective treatment in unresponsive forms of GCK-HI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-021-02045-3. BioMed Central 2021-10-11 /pmc/articles/PMC8507241/ /pubmed/34635134 http://dx.doi.org/10.1186/s13023-021-02045-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Maiorana, Arianna Caviglia, Stefania Greco, Benedetta Alfieri, Paolo Cumbo, Francesca Campana, Carmen Bernabei, Silvia Maria Cusmai, Raffaella Mosca, Antonella Dionisi-Vici, Carlo Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
title | Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
title_full | Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
title_fullStr | Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
title_full_unstemmed | Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
title_short | Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
title_sort | ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507241/ https://www.ncbi.nlm.nih.gov/pubmed/34635134 http://dx.doi.org/10.1186/s13023-021-02045-3 |
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