Classic Ketogenic Diet and Modified Atkins Diet in SLC2A1 Positive and Negative Patients with Suspected GLUT1 Deficiency Syndrome: A Single Center Analysis of 18 Cases

Background: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is caused by mutations in the SLC2A1 gene and produces seizures, neurodevelopmental impairment, and movement disorders. Ketogenic dietary therapies (KDT) are the gold standard treatment. Similar symptoms may appear in SLC2A1 negative patients. The purpose is to evaluate the effectiveness of KDT in children with GLUT1DS suspected SLC2A1 (+) and (-), side effects (SE), and the impact on patients nutritional status. Methods: An observational descriptive study was conducted to describe 18 children (January 2009–August 2020). SLC2A1 analysis, seizures, movement disorder, anti-epileptic drugs (AEDS), anthropometry, SE, and laboratory assessment were monitored baseline and at 3, 6, 12, and 24 months after the onset of KDT. Results: 6/18 were SLC2A1(+) and 13/18 had seizures. In these groups, the age for debut of symptoms was higher. The mean time from debut to KDT onset was higher in SLC2A1(+). The modified Atkins diet (MAD) was used in 12 (5 SLC2A1(+)). Movement disorder improved (4/5), and a reduction in seizures >50% compared to baseline was achieved in more than half of the epileptic children throughout the follow-up. No differences in effectiveness were found according to the type of KDT. Early SE occurred in 33%. Long-term SE occurred in 10, 5, 7, and 5 children throughout the follow-up. The most frequent SE were constipation, hypercalciuria, and hyperlipidaemia. No differences in growth were found according to the SLC2A1 mutation or type of KDT. Conclusions: CKD and MAD were effective for SLC2A1 positive and negative patients in our cohort. SE were frequent, but mild. Permanent monitoring should be made to identify SE and nutritional deficits.

[1]  I. Scheffer,et al.  Glut1 Deficiency Syndrome (Glut1DS): State of the art in 2020 and recommendations of the international Glut1DS study group , 2020, Epilepsia open.

[2]  Laura Andrea Puerta Macfarland,et al.  Safety and Effectiveness of the Prolonged Treatment of Children with a Ketogenic Diet , 2020, Nutrients.

[3]  P. V. van Hasselt,et al.  Glucose transporter type 1 deficiency syndrome and the ketogenic diet , 2019, Journal of Inherited Metabolic Disease.

[4]  U. Monani,et al.  Therapeutic strategies for glucose transporter 1 deficiency syndrome , 2019, Annals of clinical and translational neurology.

[5]  R. Caraballo,et al.  A Prospective Study on Changes in Nutritional Status and Growth Following Two Years of Ketogenic Diet (KD) Therapy in Children with Refractory Epilepsy , 2019, Nutrients.

[6]  A. Tagliabue,et al.  Impact of the Ketogenic Diet on Linear Growth in Children: A Single-Center Retrospective Analysis of 34 Cases , 2019, Nutrients.

[7]  E. Martín,et al.  Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1) , 2019, Neurología.

[8]  V. Castillo,et al.  [GLUT-1 deficiency syndrome]. , 2019, Revista de neurologia.

[9]  Subhasis Chaudhuri,et al.  Current State of Art , 2019, Visual and Text Sentiment Analysis through Hierarchical Deep Learning Networks.

[10]  I. Scheffer,et al.  Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group , 2018, Epilepsia open.

[11]  A. Beyerlein,et al.  10 patients, 10 years - Long term follow-up of cardiovascular risk factors in Glut1 deficiency treated with ketogenic diet therapies: A prospective, multicenter case series. , 2017, Clinical nutrition.

[12]  P. Striano,et al.  Biochemical phenotyping unravels novel metabolic abnormalities and potential biomarkers associated with treatment of GLUT1 deficiency with ketogenic diet , 2017, PloS one.

[13]  E. Kossoff,et al.  Complications During Ketogenic Diet Initiation: Prevalence, Treatment, and Influence on Seizure Outcomes. , 2017, Pediatric neurology.

[14]  C. Delanoé,et al.  Use of modified Atkins diet in glucose transporter type 1 deficiency syndrome , 2016, Developmental medicine and child neurology.

[15]  H. Oguni,et al.  Outcome of ketogenic diets in GLUT1 deficiency syndrome in Japan: A nationwide survey , 2016, Brain and Development.

[16]  E. Kossoff,et al.  Use of dietary therapies amongst patients with GLUT1 deficiency syndrome , 2016, Seizure.

[17]  M. Mahmoudi,et al.  The effects of classic ketogenic diet on serum lipid profile in children with refractory seizures , 2016, Acta Neurologica Belgica.

[18]  A. Aldenkamp,et al.  The MCT-ketogenic diet as a treatment option in refractory childhood epilepsy: A prospective study with 2-year follow-up , 2015, Epilepsy & Behavior.

[19]  A. Tagliabue,et al.  Short-term effects of ketogenic diet on anthropometric parameters, body fat distribution, and inflammatory cytokine production in GLUT1 deficiency syndrome. , 2015, Nutrition.

[20]  J. Lawson,et al.  Ten-year single-center experience of the ketogenic diet: factors influencing efficacy, tolerability, and compliance. , 2015, The Journal of pediatrics.

[21]  V. Stallings,et al.  Long‐term impact of the ketogenic diet on growth and resting energy expenditure in children with intractable epilepsy , 2014, Developmental medicine and child neurology.

[22]  Kyoko Takano,et al.  A three-year-old boy with glucose transporter type 1 deficiency syndrome presenting with episodic ataxia. , 2014, Pediatric neurology.

[23]  P. Veggiotti,et al.  GLUT1 deficiency syndrome 2013: Current state of the art , 2013, Seizure.

[24]  B. P. Warrenburg,et al.  Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet , 2013, Movement disorders : official journal of the Movement Disorder Society.

[25]  K. Rostásy,et al.  Glucose Transporter Type 1 Deficiency Syndrome Effectively Treated with Modified Atkins Diet , 2013, Neuropediatrics.

[26]  I. Skogseid,et al.  Good outcome in patients with early dietary treatment of GLUT‐1 deficiency syndrome: results from a retrospective Norwegian study , 2013, Developmental medicine and child neurology.

[27]  J. Klepper.  Absence of SLC2A1 Mutations Does Not Exclude Glut1 Deficiency Syndrome , 2013, Neuropediatrics.

[28]  Hoon-Chul Kang,et al.  Catch-up growth after long-term implementation and weaning from ketogenic diet in pediatric epileptic patients. , 2013, Clinical nutrition.

[29]  Hong Yang,et al.  Glucose transporter type I deficiency syndrome: Epilepsy phenotypes and outcomes , 2012, Epilepsia.

[30]  J. Klepper.  GLUT1 deficiency syndrome in clinical practice , 2012, Epilepsy Research.

[31]  J. Cross,et al.  The effect of the classical and medium chain triglyceride ketogenic diet on vitamin and mineral levels. , 2012, Journal of human nutrition and dietetics : the official journal of the British Dietetic Association.

[32]  B. Weschke,et al.  Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder. , 2010, Brain : a journal of neurology.

[33]  E. Kossoff,et al.  Empiric Use of Potassium Citrate Reduces Kidney-Stone Incidence With the Ketogenic Diet , 2009, Pediatrics.

[34]  E. Kossoff.  International consensus statement on clinical implementation of the ketogenic diet: Agreement, flexibility, and controversy , 2008, Epilepsia.

[35]  H. Oguni,et al.  Modified Atkins diet therapy for a case with glucose transporter type 1 deficiency syndrome , 2008, Brain and Development.

[36]  E. Kossoff,et al.  Kidney Stones and the Ketogenic Diet: Risk Factors and Prevention , 2007, Journal of child neurology.

[37]  G. Coppola,et al.  Plasma free carnitine in epilepsy children, adolescents and young adults treated with old and new antiepileptic drugs with or without ketogenic diet , 2006, Brain and Development.

[38]  E. Berry-Kravis,et al.  Changes in growth and seizure reduction in children on the ketogenic diet as a treatment for intractable epilepsy. , 2005, Journal of the American Dietetic Association.

[39]  Hong Yang,et al.  Glut‐1 deficiency syndrome: Clinical, genetic, and therapeutic aspects , 2005, Annals of neurology.

[40]  Hoon-Chul Kang,et al.  Early‐ and Late‐onset Complications of the Ketogenic Diet for Intractable Epilepsy , 2004, Epilepsia.

[41]  E. Vining,et al.  Effect of a high-fat ketogenic diet on plasma levels of lipids, lipoproteins, and apolipoproteins in children. , 2003, JAMA.

[42]  M. Parmar.  Kidney Stones, Carbonic Anhydrase Inhibitors, and the Ketogenic Diet , 2003, Epilepsia.

[43]  K. Engelstad,et al.  Seizure Characterization and Electroencephalographic Features in Glut‐1 Deficiency Syndrome , 2003, Epilepsia.

[44]  E. Vining,et al.  Growth of children on the ketogenic diet. , 2002, Developmental medicine and child neurology.

[45]  R. Schuller,et al.  Growth retardation in children with epilepsy on the ketogenic diet: a retrospective chart review. , 2002, Journal of the American Dietetic Association.

[46]  Gayle Booth,et al.  Carnitine Levels and the Ketogenic Diet , 2001, Epilepsia.

[47]  R. Chesney.  The Maintenance Need for Water in Parenteral Fluid Therapy , 1998, Pediatrics.

[48]  N. Spinner,et al.  GLUT-1 deficiency syndrome caused by haploinsufficiency of the blood-brain barrier hexose carrier , 1998, Nature Genetics.

[49]  S. Harik,et al.  Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. , 1991, The New England journal of medicine.