Research progress on inducement and pathogenesis of euglycemic diabetic ketoacidosis / 重庆医学

Euglycemic diabetic ketoacidosis(euDKA)is a rare acute metabolic disorder syndrome,its characteristics include metabolic acidosis with a high anion gap,positive ketones in blood or urine,and blood glucose＜13.9 mmol/L.Due to low blood sugar level,euDKA is easy to be missed or delayed treatment in clinical work,resulting in serious consequences.In recent years,many cases of euDKA have been reported,but its inducements and pathogenesis are not fully understood.This article reviews the common inducements and pathogenesis of euDKA.

Deficiencia del transportador de glucosa tipo 1: aspectos clínicos, diagnóstico y terapéutica / Glucose transporter type 1 deficiency syndrome: clinical aspects, diagnosis, and treatment

El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.

Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid, and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.

Research progress of exogenous ketone body 3-hydroxybutyrate supplementation for human disease treat-ment / 实用医学杂志

3-hydroxybutyrate(3HB),an anionic small molecule acid metabolite with a hydroxyl group,is a chiral molecule that exists in two enantiomeric forms.It is associated with cell growth,proliferation,and anti-oxida-tive stress,and demonstrates good biosafety when used within a specific range.In addition to epilepsy treatment,with the popularity of ketogenic diet in recent years,exogenous supplementation of 3HB for human has been gradu-ally found to be associated with a variety of metabolic diseases.This review describes the physiological function,physicochemical characteristics,toxicology and biological safety of 3HB,and its applications as potential drug mol-ecules in epilepsy,weight-loss(or weight control),systemic inflammation,hemorrhagic shock,cancer,inflammatory bowel disease,atherosclerosis,diabetes,osteoporosis,neurological diseases(e.g.,Parkinson's disease,Alzheimer's disease and Huntington's disease),muscular dystrophy,COVID-19,anti-aging and many other medical fields.This review also focuses on the discussion and prospect of the new methods and the potential limitations of exogenous 3HB supplementation for clinical transformation.

Ketogenic diet in the treatment of polycystic ovary syndrome / 中华内分泌代谢杂志

The ketogenic diet, a non-pharmacotherapy, simulates the state of fasting to induce the liver to metabolize fatty acids into ketones as fuel source. It also possesses anti-inflammatory effects and impacts the occurrence and progression of various diseases among which is polycystic ovary syndrome(PCOS). Ketogenic diet effectively manages body weight, improves ovarian function, regulates metabolic disorder, and enhances mental health. The growing body of evidence substantiates the safety and efficacy profile.

Ketogenic diet therapy for glucose transporter type 1 deficiency syndrome with food allergies: a case report / 中华临床营养杂志

The development of genetic testing technology has allowed the increasing diagnosis of inherited metabolic diseases. The principle of treatment of inherited metabolic diseases is to limit the intake of the substrates of a reaction that is impaired, reduce the accumulation of harmful metabolites, and replenish insufficient metabolites. Common inherited metabolic diseases include amino acid and peptide metabolism disorders, lipid and lipoprotein metabolism disorders, fatty acid and ketone metabolism disorders, carbohydrate metabolism disorders, and other metabolic disorders. Therefore, fine modification on the ratios of nutrients is required in the clinical nutrition treatment for such diseases. The commonly used approach is diet intervention. Here we report a case of a child with glucose transporter type 1 deficiency syndrome, who received the whole course nutritional management with dietary nutrient ratio modification, and discuss the role of ketogenic diet in this disease and its implementation. We aim to explore the significance of individualized dietary therapy in improving the prognosis and quality of life in children with inherited metabolic diseases.

Anti-inflammatory immunotherapy in febrile infection-associated epilepsy syndrome / 中国神经精神疾病杂志

Febrile infection-related epilepsy syndrome(FIRES)is a lethal encephalopathy with refractory status epilepticus as the main manifestation,and the selection of effective antiepileptic drugs(AEDs)is the focus and difficulty of treatment.This review summarises the mechanism of action,drug administration and adverse effects of different anti-inflammatory immunotherapies in the treatment of this disease,and finds that early initiation of ketogenic diet(KD)is one of the most effective treatments at present,and further studies are needed to clarify the adverse effects of the drugs and the effects of the combination of different drugs.

Research progress on the influence of a ketogenic diet on athletic performance and fatigue recovery / 中国实验动物学报

Ketogenic diet can supplement blood ketone,provide energy for skeletal muscle,and affect the athletic performance and recovery of animals and humans after fatigue.In this paper,it was found that ketogenic diet transformed muscle fibers from Ⅱb to Ⅱa through axonal germination and nerve reinnervation,improved the quality and function of mitochondria of fast muscle and increased histone acetyltransferase to enhance skeletal muscle strength.Using ketone body to provide energy,it can reduce glycolysis and improve the ability of fatty acid oxidation in slow muscle to improve exercise endurance;It can reduce endoplasmic reticulum stress,oxidative stress and inflammatory reaction of skeletal muscle,protect the body from injury,reduce the consumption of muscle glycogen and the accumulation of lactic acid,reduce fatigue after exercise and promote recovery.It is considered that ketogenic diet has low negative effects on the body,can improve sports performance and accelerate fatigue recovery,and can be used as a diet scheme in competitive sports and rehabilitation training.

Progress on adverse reactions and prevention and treatment of ketogenic diet therapy / 国际儿科学杂志

Ketogenic diet(KD)is a formulation diet with a high proportion of fat, low proportion of carbohydrates, appropriate protein and other nutrients, which has been used for centuries in the treatment of refractory epilepsy.In recent years, KD has been shown to be effective in the treatment of other diseases, such as amyotrophic lateral sclerosis, traumatic brain injury, diabetes, obesity, etc.Although KD has a positive effect on the treatment of a variety of diseases, the short-term and long-term adverse reactions caused by the imbalance of its nutritional structure should not be ignored.This article reviews the adverse reactions of KD in the treatment of children with refractory epilepsy and the corresponding prevention and treatment measures, to guide safe and efficient implementation of KD therapy in the clinic.

Progress of ketogenic diet on treatment of infantile spasms / 国际儿科学杂志

Infantile spasms(IS)is an age-dependent severe epilepsy syndrome, mainly treated with hormones and anti-seizure medications.However, due to poor efficacy and even serious side effects among some pediatric patients, searching for better alternative treatment options has become a research hotspot.In recent years, as a special diet treatment, ketogenic diet(KD)has been widely studied and gradually applied to the clinical treatment of IS, which has achieved satisfactory results.This article briefly reviews the KD regimen and mechanism of action, and focuses on the research progress in efficacy, safety and short-term prognosis of KD in the treatment of IS, whose purpose is to provide effective reference for clinical application.

Application of low glycemic index treatment in children with refractory epilepsy / 中华实用儿科临床杂志

Ketogenic diet (KD) has been applied to the treatment of epilepsy for the last century, although it has been underestimated due to the complicated preparation for beginners and the emergence of antiepileptic drugs.Due to the limitations of the mechanism of drug treatment of epilepsy, and the pathogenesis of epilepsy is complex, the incidence of drug-resistant epilepsy has not improved with the development of drugs over the years.KD plays an anti-epileptic and neuroprotective role through a variety of mechanisms, which is also effective to refractory epilepsy.As a result, KD has been emphasized again.Classical KD has high fat content and complicated operation.When the training is not fine enough, many patients cannot understand and qualify the operation.To overcome the disadvantages of the conventional KD, a modified KD has been developed that is closer to a normal diet structure and has a good tolerance, namely the low glycemic index treatment (LGIT). LGIT is featured by a slightly higher intake of carbohydrates, simplified meal preparation, improved taste and tolerance.This review aims to describe the mechanism, clinical outcomes and indications of LGIT in children with refractory epilepsy.

Advance in application and efficacy of ketogenic diet therapy in drug-resistant epilepsy caused by gene mutation / 国际儿科学杂志

Genetic factors are important causes of drug-resistant epilepsy.In most cases, epilepsy caused by gene mutation cannot be controlled by existing antiepileptic drugs.Ketogenic diet controls seizures through multi-target mechanism, which is widely used in the treatment of drug-resistant epilepsy caused by gene mutation.In this paper, the advance in application and efficacy of ketogenic diet therapy in 23 kinds of gene mutation related drug-resistant epilepsy is reviewed, which involves energy metabolism, ion channel, mTOR signaling pathway and some other rare diseases.

Ketogenic diet improves pancreatic β-cell dedifferentiation in db/db mice / 中华内分泌代谢杂志

Objective:To evaluate the effects of ketogenic diet(KD) on pancreatic β-cell dedifferentiation in db/db mice.Methods:In animal study, 8-week-old db/db male mice with type 2 diabetes mellitus(T2DM) were randomly divided into 3 groups: T2DM model group(ND), KD group, 75% caloric restriction(CR) group, and male C57BL/6 mice of the same age as normal control group(C) fed with standard diet. Both C and ND groups were on ad lititum feeding of chow, the KD group was free to eat the ketogenic diet, and the CR group was the positive control group, consuming 75% of the calories of the ND group every day. Four weeks after different diet intervention, body weight, fasting blood glucose, fasting insulin, glucose tolerance and blood β-hydroxybutyric acid(BHB) were measured. Morphology and structure of pancreatic islet was observed by hematoxylin-eosin staining(HE). Immunofluorescence co-staining was used to observe the expression of mouse pancreatic β-cell specific transcription factors.Results:After 4 weeks diet intervention, the fasting blood glucose, insulin and the area under the curve of blood glucose in KD group was significantly decreased( P<0.05); When compared with ND group, the morphology and structure of the islets in the KD group were more regular, and the number of islet cells increased as revealed with HE staining. Pancreatic immunofluorescence co-assay showed that KD not only restored the number and arrangement of β-cells and the ratio of β/α-cell in the pancreatic islets, but also reversed the expression of specific β-cell transcription factors such as pancreatic duodenal homeobox factor-1(PDX1). Conclusion:KD can reduce fasting blood glucose, fasting insulin and improve glucose tolerance in db/db mice, which may be related to its ability to restore the expression of specific β-cell transcription factors and reverse the dedifferentiation of pancreatic β-cells.

Efficacy and safety of modified Atkins diet in children with global developmental delay: a multicenter clinical study / 中华实用儿科临床杂志

Objective:To evaluate the efficacy and safety of modified Atkins diet (MAD) in treating global growth retardation (GDD).Methods:A prospective multicenter clinical controlled study was conducted.The children were included from 8 departments of children′s rehabilitation in Henan Province from July 2017 to October 2017.A total of 154 children who met the inclusion criteria were randomly assigned into the routine treatment group (88 cases) and MAD therapy group (66 cases). A total of 62 children in MAD therapy group and 59 children in routine treatment group completed the study for 15 months.The routine treatment group was provided comprehensive rehabilitation training, and the MAD therapy group was given MAD treatment on the basis of rehabilitation training.Two-way repeated-measures ANOVA was used to compare the differences among datas at different time points. Results:After 3 months, there were significant differences in the scores of the Chinese Version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA)/Achenbach Children′s Behavior Scale (CBCL) between the 2 groups (all P<0.05). Significant improvement was seen in the MAD group.After 6 months, the MAD therapy group had significantly higher scores on the Gesell Developmental Scale for language and social behavior than the routine treatment group (all P<0.05). After 9 months, the scores of the children in the MAD therapy group were better than those in the routine treatment group in the Gesell Developmental Scale adaptive energy area and the infant-junior high school student social life scale (S-M scale), and the differences were statistically significant (all P<0.05). After 15 months, the fine motor in the MAD therapy group was better than that in the routine treatment group ( P<0.05). At the early stage of MAD therapy, 28 patients showed mild adverse reactions that were reversed after symptomatic treatment.No severe adverse reactions were observed. Conclusions:MAD therapy can improve the neuro-development, emotional and social behaviors, and adaptive behaviors with no severe adverse effects.

Decreased ovarian reserve and ovarian morphological alterations in female rat offspring exposed to a ketogenic maternal diet

SUMMARY OBJECTIVE: This study evaluates the effects of a ketogenic diet on morphology and follicle reserve. METHOD: Sixteen Sprague-Dawley rats were randomized into two groups: standard diet group (n=8) and ketogenic diet group (n=8). Rats were time mated. Dams were permitted to deliver spontaneously. The animals were monitored for the onset of puberty. All the rats were weighed and anesthetized, serum anti-Müllerian hormone level was measured, and the oviducts were removed. The morphological characteristics of follicles were determined and total ovarian volumes were calculated. RESULTS: The mean ovarian volume was statistically significantly lower in the ketogenic diet group compared to the standard diet group (14.41±0.99 mm3 versus 18.89±1.28 mm3) (p=0.000). The mean number of antral follicles was 13.63±1.80 in the standard diet group and 4.462±0.760 in the ketogenic diet group. The mean ovarian weight of the ketogenic diet group was significantly lower than that of the standard diet group (0.42±0.06 g versus 0.815±107 g). The mean anti-Müllerian hormone levels were significantly higher in the standard diet group compared to the ketogenic diet group (1.023±4.75 ng/mL versus 0.69±0.07 ng/mL) (p=0.000). The mean percentage of staining of Ki-67 was 35.28±4.75 in the standard diet group and 16.98±3.33 in the ketogenic diet group (p=0.000). CONCLUSION: Maternal ketogenic diet reduces ovarian follicular reserve in female offspring and has important implications for maintaining reproductive potential at a population level.

Research progress of anti-inflammatory mechanism of ketogenic diet / 中华实用儿科临床杂志

Composed by high fat, low carbohydrate, adequate protein and other nutrients, ketogenic diet (KD) is a kind of diet.KD simulates starvation has fatty acid metabolism to produce ketone body, thus providing energy in liver, and it has various functions such as anti-inflammation.KD has been used in nervous system diseases, but its mechanism is still not very clear.As a result, the review expounds KD mechanism of anti-inflammatory action from the inhibition of pathogenic microorganisms, adjusting intestinal flora, relieving pain and reducing oxidative stress in several aspects.

Research progress of ketogenic diet therapy for epilepsy associated with tuberous sclerosis complex / 中华实用儿科临床杂志

Tuberous sclerosis complex (TSC) is a hereditary and multisystemic disease, caused by mutations in the TSC1 or TSC2 gene, with an incidence of about 1/14 000 to 1/6 000.The neurological manifestations of TSC often include epilepsy, developmental delay, mental disorders and loss of neurological function.Among them, epilepsy is the most common manifestation, with an incidence of 80%-90%, 55%-62% of which is drug-resistant epilepsy.Epilepsy in TSC severely affects the clinical prognosis and life quality of patients.At present, epilepsy in TSC can be treated with the inhibitors of mammalian target of rapamycin(mTOR), antiepileptic drugs, ketogenic diet(KD), neuromodulation, palliative or resection operation.Although the exact mechanism of KD in the treatment of epilepsy in TSC is not clearly elucidated yet, it has been demonstrated in some studies that it is related to the inhibition of mTOR signaling pathway and other multiple mechanisms.Meanwhile, the safety and efficacy of KD therapy have been proven in many clinical studies.Therefore, KD is recommended for the treatment of epilepsy in TSC, especially when epilepsy is resis-tant to antiepileptic drugs, is not indicated for surgery or the surgery is ineffective.The research progress of the mechanism and clinical efficacy of KD therapy for epilepsy in TSC would be reviewed in this paper.

Projeto piloto de implantação de uma cozinha cetogênica para tratamento de epilepsia refratária / Pilot project of Implementation of a keto-kitchen for the treatment of refractory epilepsy / Proyecto piloto para implementar una cocina cetogénica para el tratamiento de la epilepsia refractaria

Objetivo: verificar alterações no consumo alimentar e hábitos de vida em pacientes com fibrose cística brasileiros durante o período de isolamento social devido a pandemia de COVID-19. Métodos: pesquisa transversal com levantamento de dados por meio de questionário elaborado pela equipe de nutricionistas especialistas no tratamento de pacientes com fibrose cística, com questões referentes às manifestações respiratórias recentes de pacientes ou familiares, alterações nos hábitos de aquisição e compras de alimentos e alterações quanto ao consumo de grupos alimentares e suplementos. Os dados foram tabulados e foi realizada uma análise descritiva. Resultados: 40,34% das famílias de pacientes com fibrose cística mudaram os hábitos de compras de alimentos, cerca de 40% dos pacientes diminuíram a prática de atividade física e aumentaram o tempo de uso de telas em mais de 50% durante o período da pandemia de COVID-19. Conclusões: Apesar de algumas dificuldades relacionadas à aquisição dos alimentos e alterações em hábitos de vida, houve manutenção do consumo alimentar da maioria dos grupos alimentares e suplementos pelos pacientes pediátricos com fibrose cística brasileiros durante o isolamento social devido a pandemia de COVID-19

Objective: This study describes the creation of the first ketogenic diet-teaching kitchen at a ketogenic reference center in Brazil aimed at developing ketogenic recipes and holding keto-culinary workshops with caregivers. Method: In this prospective study, 26 recipes were tested and assessed by sensory panel testing. Eighteen recipes were selected to be prepared in culinary workshops with parents or legal guardians of children with refractory epilepsy receiving the ketogenic diet as outpatients. All recipes were selected, calculated, and approved by registered dietitians. Results: Eight parents or legal guardians participated in four culinary workshops. The activities were extremely satisfactory: participants were able to clear out their doubts, learn, practice recipes, and develop new skills. In general, all participants enjoyed the prepared recipes and praised the culinary workshop. Conclusion: The ketogenic teaching kitchen enabled the development of ketogenic recipes adapted to Brazilian eating habits. Providing alternative meals to children is essential for enhancing compliance with the ketogenic diet because they contribute to expand the dietary repertoire of these patients. Future studies with high methodological quality should test the efficacy of the ketogenic kitchen in increasing compliance with the ketogenic diet in the long term.

Objetivo: Este estudio describe la creación de la primera cocina cetogénica para enseñar dieta cetogénica en un centro de referencia en Brasil, con el objetivo de desarrollar recetas cetogénicas y realizar talleres culinarios con los cuidadores. Método: En este estudio prospectivo, un panel sensorial probó y evaluó 26 recetas. Se seleccionaron dieciocho recetas para ser elaboradas en talleres de cocina con padres o tutores legales de niños con epilepsia refractaria que reciben una dieta cetogénica ambulatoria. Todas las recetas fueron seleccionadas, calculadas y aprobadas por nutricionistas. Resultados: Ocho padres o tutores participaron en cuatro talleres culinarios. Las actividades fueron sumamente satisfactorias: los participantes pudieron despejar sus dudas, aprender, practicar recetas y desarrollar nuevas habilidades. En general, a todos los participantes les gustaron las recetas elaboradas y elogiaron el taller de cocina. Conclusión: La cocina de enseñanza cetogénica permitió el desarrollo de recetas cetogénicas adaptadas a los hábitos alimentarios brasileños. Proporcionar comidas alternativas a los niños es fundamental para mejorar la adherencia a la dieta cetogénica, ya que contribuyen a ampliar el repertorio dietético de estos pacientes. Los estudios futuros con alta calidad metodológica deberían probar la efectividad de la cocina cetogénica para aumentar la adherencia a la dieta cetogénica a largo plazo.

Dieta Cetogénica en el paciente con epilepsia refractaria / Ketogenic Diet in patients with refractory epilepsy

INTRODUCCIÓN: La epilepsia afecta a 0,5% a 1% de la población, iniciándose en la infancia en el 60% de los casos. El 25% de los niños que la presentan, tienen epilepsia refractaria (ER) a fármacos antiepilépticos (FAE) y en ellos la dieta cetogénica (DC) surge como un tratamiento no farmacológico efectivo. OBJETIVO: Evaluar el impacto de la DC en el número de crisis, en la calidad de vida y bienestar del paciente y su entorno. PACIENTES Y MÉTODO: Se revisaron los registros médicos de los pacientes con diagnóstico de ER que recibieron DC entre los años 2008 y 2018 registrando variables: edad, diagnóstico, número de crisis, número de FAE, respuesta y complicaciones. La DC se inició en todos los casos con el paciente hospitalizado durante un período no mayor a siete días, en el cual se realizó evaluación nutricional antropométrica con medición de peso y talla según condición clínica. RESULTADOS: Se analizaron 35 DC. La mediana de edad al inicio fue 4,8 años con rango intercuartil (RIC) de 2,3-6,8 años. Se utilizó DC clásica en 49% de los pacientes, Dieta Atkins Modificada en 37% y Dieta de Bajo Índice Glicémico en 14%. Su promedio de duración fue 13 meses + 11 DS meses. Luego de tres meses de iniciada la DC, la reducción de al menos un 50% de las crisis se observó en 82% de los casos, de los cuales 22,8% presentaron reducción de más de 90% y 20% quedó libre de crisis. Se registraron efectos secundarios en 21 pacientes, la mayoría gastrointestinales (62%) y dislipidemia (14%). Todos los efectos secundarios se resolvieron con manejo médico. CONCLUSIONES: La DC es un tratamiento efectivo en pacientes pediátricos con ER y las complicaciones asociadas fueron fácilmente controla das por un equipo multidisciplinario.

INTRODUCTION: Epilepsy affects 0.5 to 1% of the population. 25% of pediatric patients have drug-resistant epilepsy (DRE). Ketogenic Diet (KD) emerges as an effective, non-pharmacological treatment in this group. OBJECTIVE: To describe the effect of KD on seizure control and nutritional status in children whit DRE. PATIENTS AND METHOD: We reviewed the medical records of patients with DRE treated with KD, between 2008 and 2018, evaluating age, diagnosis, number of seizures, number of antiepileptic drugs used, clinical outcomes, and complications. The KD was initiated in all patients hospitalized for a period no longer than seven days, who were evaluated for their nutritional and anthropometric sta tus, with weight and height measurements according to the clinical condition. RESULTS: We analyzed 35 KD in 33 cases. The median age of KD initiation was 4.8 years with an interquartile range (IQR) of 2-3 to 6.8 years. Classical KD was used in 49% of patients, Modified Atkins Diet (MAD) in 37%, and Low-Glycemic Index Treatment (LGIT) in 14% of cases. The average duration was 13 months (SD 11 months). After three months of using KD, we observed at least 50% reduction of seizures in 82% (27/33) of the patients, out of these, 22.8% presented 90% or more reduction of seizures, and 20% ended up seizure-free. Adverse events were observed in 21 patients, mainly gastrointestinal (62%) and dyslipidemia (14%), without effect on height. All side effects resolved with medical ma nagement. CONCLUSIONS: KD is a useful treatment in pediatric patients with DRE without nutritional impact. The adverse events were easily controlled if the patients are evaluated by a multidisciplinary team, according to international guidelines.

Variabilidad fenotípica del déficit de GLUT1: ¿Cuándo es necesario sospechar? / Phenotypic variability of GLUT1 deficiency: when is necessary to suspect?

Resumen: Introducción: La deficiencia del transportador de glucosa tipo 1 constituye un síndrome (SD-GLUT1), provocado por la mutación del gen SLC2A1, que codifica la proteína transportadora de glucosa al encéfalo. Las manifestaciones neurológicas se dan en tres dominios principales: crisis epilépticas, movimientos anormales y alteraciones cognitivas. El diagnóstico se presume ante el hallazgo de hipoglucorraquia y se confirma mediante el análisis molecular del gen. La importancia de precisarlo radica en que tiene tratamiento específico, la dieta cetogénica. Objetivo: Analizar dos casos clínicos de SD-GLUT1 de presentación atípica, destacando la variabilidad del fenotipo. Caso Clínico: Presentamos el caso de dos hermanos cuyas manifestaciones fueron crisis epilépticas de tipo ausencias típicas, y un trastorno paroxístico del movimiento. Los pacientes fueron estudiados encontrándose hipoglucorraquia en ambos y se confirmó diagnóstico de SD-GLUT1 con estudio molecular. El tratamiento específico con dieta cetogénica logró buena respuesta. Conclusiones: Exponemos sus características clínicas peculiares que nos permitieron sospechar este cuadro, de espectro fenotípico amplio, cuyo diagnós tico y tratamiento, correcto y oportuno, puede mejorar significativamente la calidad de vida de los afectados.

Abstract: Introduction: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1-DS) is caused by the SLC2A1 gene muta tion, which encodes the glucose transporter proteins to the brain Neurological manifestations occur in three main domains: seizures, abnormal movements, and cognitive disorders. The diagnosis is presumed upon the finding of low CSF glucose and confirmed by the gene molecular analysis. Ac curate diagnosis is important because it has a specific treatment, which is ketogenic diet. Objective: To analyze two SD-GLUT1 pediatric patients with unusual phenotype. Clinical Case: We present the case of two siblings who presented absence seizures and a paroxysmal movement disorder. Both patients were studied, finding low CSF glucose. The diagnosis of GLUT1-DS was confirmed with molecular analysis. Specific treatment with ketogenic diet achieved good response in both cases. Con clusions: We present their peculiar clinical characteristics that allowed us to suspect this wide phe notypic spectrum. Correct and timely diagnosis and treatment can significantly improve the quality of life of those affected.

Dieta cetogénica: mecanismos en el control de la epilepsia refractaria / Ketogenic diet: refractory epilepsy control mechanisms

Introducción: Existe un porcentaje relevante de pacientes con epilepsia que son refractarios al tratamiento con fármacos anticonvulsivan-tes. Este cuadro, se denomina epilepsia refractaria (ER), en el cual, la dieta cetogénica (DC), ha probado ser una alternativa efectiva. Existen diferentes versiones de la DC, y ciertos componentes de esta dieta han mostrado ser más efectivos que otros. Por otra parte, diferentes autores han propuesto hipótesis, de cómo, la DC podría actuar a nivel molecular y celular, para controlar estas crisis epilépticas. Los objetivos de esta revisión, son, explicar la DC, y analizar la evidencia existente, en relación con los mecanismos, a través de los cuales, la DC ejerce un control de las crisis convulsivas. Método y resultados: Se realizó una búsqueda avanzada en PubMed, considerando los términos «refrac-tory¼, «epilepsy¼, «ketogenic¼ y «diet¼, incluidos en el título y el resumen. La búsqueda, dio como resultado, 288 artículos publicados en los últimos 10 años. De estos artículos, se seleccionaron 134 potencialmente relevantes, posterior a la lectura de sus títulos. Se realizó la lectura del resumen para los 134 artículos, de los cuales, se seleccionaron 17, que fueron, a juicio de los autores, los que incluían la información pertinente para esta revisión. La búsqueda se centró en artículos originales y revisiones disponibles en inglés,con énfasis, en los artículos apropiados para comprender los conceptos generales de la DC y los mecanismos de acción, que podrían representar un rol relevante al momento de controlar la ER. Conclusiones: La DC ha probado ser efectiva en el tratamiento de la ER, sin embargo, hay pacientes que no la toleran adecuadamente. Existen ciertos compuestos asociados la DC que han probado ser más efectivos que otro como es el caso de los triglicéridos de cadena mediana (TCM). Finalmente, se han investigado numerosas hipótesis en relación con el mecanismo de acción de la DC, donde destacan las hipótesis de los cuerpos cetónicos, la adenosina y la del cortocircuito GABA.

Introduction: A percentage of epilepsy patients are refractory to treatment with anticonvulsant drugs. An effective alternative for treating this condition, known as refractory epilepsy (RE), is the ketogenic diet (KD). There are different variations of the KD, and certain components of this diet have been shown more effective than others. Various authors have proposed hypotheses for how the KD acts on the molecular and cellular levels in controlling seizures. The objectives of this review are to explain the KD and analyze existing evi-dence regarding the mechanisms through which the KD exercises control over seizures. Methods and results: PubMed was extensively searched using the terms «refractory¼, «epilepsy¼, «ketogenic¼, and«diet¼ included in the title and abstract. The search returned 288 published articles within the last ten years. Of these 288 manuscripts, 134 were selected as potentially relevant based on the title. After reading the abstract of each potentially relevant paper, 17 were finally included in the review. These manuscripts, per the judgement of the authors of this study, included information pertinent to the review. The search focused on original articles and reviews available in English, with an emphasis on texts appropriate for understanding the general concepts of the KD and the mechanisms of action that could play a relevant role in controlling RE. Conclusions: The KD has been proven effective in treating RE. However, some patients do not adequately tolerate this diet. There are certain compounds associated with the KD that are more effective than others, as is the case with medium-chain triglycerides. Finally, numerous hypotheses exist regarding the mechanisms of action for the KD. Notable among these hypotheses are ketone bodies, adenosine, and the GABA shunt.