Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations
Abstract 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. Patie...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-02045-3 |
| _version_ | 1818743937775435776 |
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| author | Arianna Maiorana Stefania Caviglia Benedetta Greco Paolo Alfieri Francesca Cumbo Carmen Campana Silvia Maria Bernabei Raffaella Cusmai Antonella Mosca Carlo Dionisi-Vici |
| author_facet | Arianna Maiorana Stefania Caviglia Benedetta Greco Paolo Alfieri Francesca Cumbo Carmen Campana Silvia Maria Bernabei Raffaella Cusmai Antonella Mosca Carlo Dionisi-Vici |
| author_sort | Arianna Maiorana |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-18T02:36:21Z |
| format | Article |
| id | doaj.art-32f1fba12d5b4d319b99ec69ba95c3ea |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-18T02:36:21Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-32f1fba12d5b4d319b99ec69ba95c3ea2022-12-21T21:23:46ZengBMCOrphanet Journal of Rare Diseases1750-11722021-10-0116111010.1186/s13023-021-02045-3Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutationsArianna Maiorana0Stefania Caviglia1Benedetta Greco2Paolo Alfieri3Francesca Cumbo4Carmen Campana5Silvia Maria Bernabei6Raffaella Cusmai7Antonella Mosca8Carlo Dionisi-Vici9Division of Metabolism, Department of Pediatric Subspecialties, Ospedale Pediatrico Bambino Gesù, IRCSSPsychology Clinic Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCSPsychology Clinic Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCSChild and Adolescent Psychiatric Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCSChild and Adolescent Psychiatric Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCSDivision of Metabolism, Department of Pediatric Subspecialties, Ospedale Pediatrico Bambino Gesù, IRCSSDivision of Artificial Nutrition, Ospedale Pediatrico Bambino Gesù, IRCCSNeurology Unit, Department of Neuroscience, Ospedale Pediatrico Bambino Gesù, IRCCSDepartment of Hepatology, Gastroenterology and Nutrition, Ospedale Pediatrico Bambino Gesù, IRCCSDivision of Metabolism, Department of Pediatric Subspecialties, Ospedale Pediatrico Bambino Gesù, IRCSSAbstract 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.https://doi.org/10.1186/s13023-021-02045-3Hyperinsulinemic hypoglycemiaKetogenic dietHypoglycemiaNeurodevelopmentCognitive outcomeEpilepsy |
| spellingShingle | Arianna Maiorana Stefania Caviglia Benedetta Greco Paolo Alfieri Francesca Cumbo Carmen Campana Silvia Maria Bernabei Raffaella Cusmai Antonella Mosca Carlo Dionisi-Vici Ketogenic diet as elective treatment in patients with drug-unresponsive hyperinsulinemic hypoglycemia caused by glucokinase mutations Orphanet Journal of Rare Diseases Hyperinsulinemic hypoglycemia Ketogenic diet Hypoglycemia Neurodevelopment Cognitive outcome Epilepsy |
| 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 | Hyperinsulinemic hypoglycemia Ketogenic diet Hypoglycemia Neurodevelopment Cognitive outcome Epilepsy |
| url | https://doi.org/10.1186/s13023-021-02045-3 |
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