Stroke and Stroke-Like Episodes: Recurrent Manifestations in GLUT1 Deficiency Syndrome.

BACKGROUND: Since the initial description of glucose transporter-1 deficiency syndrome (Glut1-DS) the phenotype of the condition has expanded, even leading to the recognition of atypical manifestations. We report on eight patients with Glut1-DS who experienced at least one episode of acute focal neurological deficits. METHODS: We conducted a retrospective analysis, collecting clinical, electrophysiological, neuroradiological, and genetic information. We focused in particular on three well-documented cases. RESULTS: Among 42 patients with Glut1-DS, eight individuals aged between six and 38 years presented with an acute onset of neurological disturbances: dysarthria/aphasia, oral dyskinesia, swallowing difficulties, paresthesia, facial palsy, hemi/monoplegia, vomiting, headache, and behavioral disturbances. When performed, magnetic resonance imaging (MRI) revealed signs of venous congestion and hypoperfusion and electroencephalography showed focal contralateral slowing. Deficits were transient in all patients but one. Four patients (50%) were on a ketogenic diet (KD), and two of these patients had lower than usual ketonemia levels during the episode. In two patients, MRI demonstrated the presence of an ischemic brain lesion. CONCLUSIONS: In Glut1-DS, stroke-like episodes are a recurrent manifestation, particularly during early adulthood, and they were reported in 19% of the patients in our cohort. Stroke mimics should be considered a key feature of Glut1-DS, as other paroxysmal disorders. It remains to be established whether a KD can prevent the recurrence of episodes and, if so, at what level of ketosis. Further observations are needed to confirm the correlation between Glut1-DS and ischemic stroke.

GLUT1DS focus on dysarthria.

RESEARCH PURPOSE: GLUT1 deficiency syndrome (GLUT1DS) is a rare genetic disorder caused by a mutation in the SLC2A1 gene that limits the transport of glucose across the blood-brain barrier. Speech disorders and dysarthria are typical findings in patients with GLUT1DS, but have never been deeply phenotyped. The aim of the present study was to characterize speech abilities in a sample of patients with GLUT1DS. RESULTS: 30 patients with GLUT1DS were recruited. We reported impairments in different speech and oromotor domains: the speech was characterized by dysarthria, inaccurate articulation of consonants, abnormal nasal resonance, errors in intonation and prosody and low intelligibility. We observed difficulties in motor planning and programming. Moreover, we observed a significant difference between the dysarthric level of impairment with genotype groups. CONCLUSIONS: The presence of a speech disorder in patients with GLUT1DS represents a core feature of the syndrome. Our findings suggest that patients with GLUT1DS would benefit from a comprehensive neurocognitive assessment to detect strengths and weaknesses of the speech profile. Understanding the speech and language phenotype in GLUT1DS is critical for planning early intervention to positively influence the global development of patients with GLUT1DS.

Differentiating non-epileptic seizures from epileptic seizures in Glut1 deficiency syndrome.

AIM: To investigate the clinical characteristics of non-epileptic seizures due to transient brain dysfunction caused by energy deficiency after prolonged fasting or exercise in individuals with glucose transporter type 1 deficiency syndrome (Glut1DS), and then elucidate further the seizure features to distinguish non-epileptic seizures from epileptic seizures. METHOD: This retrospective case-control study included 57 non-epileptic seizures and 23 epileptic seizures (control group) in 14 individuals (11 males, three females; aged 5-44 years, median = 20 years) with Glut1DS, all with a heterozygous pathogenic SLC2A1 mutation. RESULTS: Non-epileptic seizures were classified as paroxysmal altered consciousness (n = 8), movement disorders (n = 35) (eye-head movements, ataxia, spasticity, weakness, involuntary movement), dysaesthesia (n = 8), and vomiting (n = 6) at the peak ages at onset of 5 to 10 years. Ketogenic diet therapy was effective in 33 of 43 (77%) non-epileptic seizures. Providing supplementary food before high-impact exercise or during attacks prevented or mitigated non-epileptic seizures in some individuals. Glut1DS-associated non-epileptic seizures are fundamentally situation-related seizures with specific provoking and ameliorating factors. Non-epileptic seizures can be distinguished from epileptic seizures by the absence of complete consciousness loss and rapid postictal recovery despite prolonged seizures. INTERPRETATION: Non-epileptic seizures are not well recognized but require different therapeutic approaches compared to epileptic seizures. Awareness of the differentiation of non-epileptic seizures from epileptic seizures is essential when performing preventive or therapeutic decision-making for acute exacerbation seizures. WHAT THIS PAPER ADDS: Non-epileptic seizures are invariably situation-related seizures. Non-epileptic seizures were classified as altered consciousness, movement disorders, dysaesthesia, and vomiting. Non-epileptic seizures were characterized by the absence of complete consciousness loss and were accompanied by rapid recovery. Non-epileptic seizures can occur simultaneously or consecutively with another. Supplementary food can be effective in preventing the development of sustained exercise-induced movement disorders.

[Triose phosphate isomerase deficiency: a rare erythrocyte enzymopathy with a poor prognosis]. / Le déficit en triose phosphate isomérase : une enzymopathie érythrocytaire rare et de pronostic sombre.

Triose phosphate isomerase (TPI) is a crucial enzyme for glycolysis. TPI deficiency is an autosomal recessive metabolic disease described in 1965, which remains exceptional by its rarity (less than 100 cases described worldwide), but by its extreme severity. Indeed, it is characterized by a chronic hemolytic anemia, an increased susceptibility to infections and especially, a progressive neurological degeneration which leads to death in early childhood for the majority of cases. We report in our observation the history of diagnosis and clinical course of monozygotic twins born at 32 WA with triose phosphate isomerase deficiency.

[Hemidystonia and hemichorea in a pediatric patient with glucose transporter type 1 deficiency]. / Hemidistonía y hemicorea en un paciente pediátrico con déficit del transportador de glucosa de tipo 1.

Glucose transporter type 1 deficiency syndrome is a rare pediatric neurometabolic disorder. There are two phenotypes: the classical phenotype (85%) and the non-classic (15%). Both phenotypes are associated with hypoglycorrhachia. Multiple mutations are described in the SCL2A1 gene. The treatment is the ketogenic diet. We report a case of a four-year-old male patient who started with hemichorea and hemidystonia and was medicated with drugs for seizures without clinical response, that's why his parents made another pediatric consultation at his six-year-old. With the suggestive clinical findings of glucose transporter type 1 deficiency syndrome the lumbar puncture was made confirming the diagnosis. Immediately after starting the ketogenic diet the patient stopped making abnormal movements up to the moment when he is fourteen years old, eight years after.

El síndrome de deficiencia del transportador de glucosa cerebral de tipo 1 es una enfermedad neurometabólica rara en pediatría. Existe un fenotípico clásico (85 %) y otro no clásico (15 %). Ambos fenotipos se asocian con hipoglucorraquia. Se identifican múltiples mutaciones en el gen SLC2A1. El tratamiento es la terapia cetogénica. Se presenta un varón que comenzó a los cuatro años con hemicorea y hemidistonía medicado con anticonvulsivantes sin respuesta clínica, por lo que consultó nuevamente a los seis años. Con sospecha diagnóstica de síndrome de déficit de glut-1 atípico se realizó punción lumbar; el diagnóstico se confirmó por la presencia de hipoglucorraquia. Inmediatamente después de iniciar la dieta cetogénica, el paciente no presentó más movimientos anormales durante los siguientes 8 años hasta la actualidad, ya cumplidos los 14 años.

Hemidistonía y hemicorea en un paciente pediátrico con déficit del transportador de glucosa de tipo 1 / Hemidystonia and hemichorea in a pediatric patient with glucose transporter type 1 deficiency

El síndrome de deficiencia del transportador de glucosa cerebral de tipo 1 es una enfermedad neurometabólica rara en pediatría. Existe un fenotípico clásico (85 %) y otro no clásico (15 %). Ambos fenotipos se asocian con hipoglucorraquia. Se identifican múltiples mutaciones en el gen SLC2A1. El tratamiento es la terapia cetogénica. Se presenta un varón que comenzó a los cuatro años con hemicorea y hemidistonía medicado con anticonvulsivantes sin respuesta clínica, por lo que consultó nuevamente a los seis años. Con sospecha diagnóstica de síndrome de déficit de glut-1 atípico se realizó punción lumbar; el diagnóstico se confirmó por la presencia de hipoglucorraquia. Inmediatamente después de iniciar la dieta cetogénica, el paciente no presentó más movimientos anormales durante los siguientes 8 años hasta la actualidad, ya cumplidos los 14 años.

Glucose transporter type 1 deficiency syndrome is a rare pediatric neurometabolic disorder. There are two phenotypes: the classical phenotype (85%) and the non-classic (15%). Both phenotypes are associated with hypoglycorrhachia. Multiple mutations are described in the SCL2A1 gene. The treatment is the ketogenic diet. We report a case of a four-year-old male patient who started with hemichorea and hemidystonia and was medicated with drugs for seizures without clinical response, that's why his parents made another pediatric consultation at his six-year-old. With the suggestive clinical findings of glucose transporter type 1 deficiency syndrome the lumbar puncture was made confirming the diagnosis. Immediately after starting the ketogenic diet the patient stopped making abnormal movements up to the moment when he is fourteen years old, eight years after.

Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome.

INTRODUCTION: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. AIMS: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. MATERIAL AND METHODS: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. RESULTS: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1 mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients with SLC2A1 mutations presented more clinical changes in relation to diet (66.7%, vs 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs 46mg/dL, P=.04) and CSF/serum glucose ratio (0.4 vs 0.48, P<.05). CONCLUSIONS: GLUT1 deficiency syndrome may be caused by mutations to genes other than SLC2A1 in patients with compatible phenotype, low CSF glucose level, and good response to the ketogenic diet.

Estudio de pacientes pediátricos con fenotipo clínico y bioquímico de síndrome de déficit de transportador de glucosa cerebral (GLUT-1) / Study of paediatric patients with the clinical and biochemical phenotype of glucose transporter type 1 deficiency syndrome

Introducción: El síndrome de déficit del transportador de glucosa cerebral (GLUT1DS) puede presentar fenotipos variados, incluyendo epilepsia, déficit intelectual y trastorno del movimiento. La mayoría presenta hipoglucorraquia y/o defectos en el gen SLC2A1, aunque existen pacientes sin hipoglucorraquia y otros con genética de SLC2A1-negativa, o con defectos en otros genes y fenotipo compatible. Objetivos: Describir las características clínicas, bioquímicas y genéticas y realizar un análisis univariante de un grupo de pacientes con fenotipo clínico y bioquímico de GLUT1DS, con o sin genética SLC2A1-positiva. Material y métodos: Se incluyeron 13 pacientes con criterios clínico-bioquímicos de GLUT1DS. Se realizó secuenciación de SLC2A1 y MLPA. En los casos negativos se realizó exoma clínico. Resultados: Seis presentaron fenotipo clásico, 2 discinesia paroxística, 2 trastornos del movimiento complejo, 2 ausencias precoces y otro presentó epilepsia con ausencias infantiles refractaria a farmacoterapia. Seis fueron SLC2A1-positivos. Y en 5 de los SLC2A1-negativos se identificó otro defecto genético. No hubo diferencias significativas entre los dos grupos en edad de inicio, presentación clínica, microcefalia, discapacidad intelectual ni respuesta a dieta cetogénica. De forma no significativa, los pacientes SCL2A1-positivos presentaron más cambios clínicos en relación con la ingesta (66,7% vs. 28,6%) y mayor persistencia de síntomas motores (66% vs. 28,6%). De forma significativa, presentaron menor glucorraquia (34,5 mg/dl vs. 46 mg/dl, p = 0,04) e índice glucorraquia/glucemia más bajo (0,4 vs. 0,48, p = 0,05) que los SLC2A1-negativos. Conclusiones: GLUT1DS puede ser causado por defectos genéticos en otros genes diferentes de SLC2A1 en pacientes con fenotipo compatible, hipoglucorraquia y buena respuesta a dieta cetogénica. (AU)

Introduction: Glucose transporter type 1 (GLUT1) deficiency syndrome may present a range of phenotypes, including epilepsy, intellectual disability, and movement disorders. The majority of patients present low CSF glucose levels and/or defects in the SLC2A1 gene; however, some patients do not present low CSF glucose or SLC2A1 mutations, and may have other mutations in other genes with compatible phenotypes. Aims: We describe the clinical, biochemical, and genetic characteristics of the disease and perform a univariate analysis of a group of patients with clinical and biochemical phenotype of GLUT1 deficiency syndrome, with or without SLC2A1 mutations. Material and methods: The study included 13 patients meeting clinical and biochemical criteria for GLUT1 deficiency syndrome. SLC2A1 sequencing and multiplex ligation-dependent probe amplification were performed; exome sequencing was performed for patients with negative results. Results: Six patients presented the classic phenotype; 2 paroxysmal dyskinesia, 2 complex movement disorders, 2 early-onset absence seizures, and one presented drug-resistant childhood absence epilepsy. Six patients were positive for SLC2A1mutations; in the other 5, another genetic defect was identified. No significant differences were observed between the 2 groups for age of onset, clinical presentation, microcephaly, intellectual disability, or response to ketogenic diet. Patients ith SLC2A1 mutations presented more clinical changes in relation to diet (66.7% vs. 28.6% in the SLC2A1-negative group) and greater persistence of motor symptoms (66% vs. 28.6%); these differences were not statistically significant. Significant differences were observed for CSF glucose level (34.5 vs. 46 mg/dL, P = .04) and CSF/serum glucose ratio (0.4 vs. 0.48, P < .05). [...] (AU)

[Food sensitivities of the digestive tract-Part 2: Food intolerances]. / Nahrungsmittelunverträglichkeiten des Verdauungstraktes ­ Teil 2: Nahrungsmittelintoleranzen.

Adverse reactions to food affect about one third of the population. They are based on very different mechanisms and are triggered by specific foods. They are divided into food intolerances, which manifest mainly in the gastrointestinal tract and food allergies, which can also cause extraintestinal symptoms and have an immunological genesis. In adults, food intolerances are significantly more common than food allergies with a prevalence of approximately 10-20%. The most important food intolerances are sugar intolerances, such as lactose and fructose intolerance but intolerances to wheat also play an increasing role. The diagnostics of food intolerances require extensive exclusion diagnostics, whereby in particular irritable bowel syndrome and intestinal dysbiosis must be differentiated. The therapy of food intolerance is primarily based on a targeted elimination diet. In this advanced education article the most important food intolerances are discussed.

Sleep Disorder: An Overlooked Manifestation of Glucose Transporter Type-1 Deficiency Syndrome.

Glucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.

GLUT1 Deficiency Syndrome-Early Treatment Maintains Cognitive Development? (Literature Review and Case Report).

Glucose transporter type 1 (GLUT1) is the most important energy carrier of the brain across the blood-brain barrier, and a genetic defect of GLUT1 is known as GLUT1 deficiency syndrome (GLUT1DS). It is characterized by early infantile seizures, developmental delay, microcephaly, ataxia, and various paroxysmal neurological phenomena. In most cases, GLUT1DS is caused by heterozygous single-nucleotide variants (SNVs) in the SLC2A1 gene that provoke complete or severe impairment of the functionality and/or expression of GLUT1 in the brain. Despite the rarity of these diseases, GLUT1DS is of high clinical interest since a very effective therapy, the ketogenic diet, can improve or reverse symptoms, especially if it is started as early as possible. We present a clinical phenotype, biochemical analysis, electroencephalographic and neuropsychological features of an 11-month-old boy with myoclonic seizures, hypogammaglobulinemia, and mildly impaired gross motor development. Using sequence analysis and deletion/duplication testing, deletion of an entire coding sequence in the SLC2A1 gene was detected. Early introduction of a modified Atkins diet maintained a seizure-free period without antiseizure medications and normal cognitive development in the follow-up period. Our report summarizes the clinical features of GLUT1 syndromes and discusses the importance of early identification and molecular confirmation of GLUT1DS as a treatable metabolic disorder.

Colonic mucosal eosinophilia in children without inflammatory bowel disease.

Children undergoing colonoscopy and mucosal biopsies may show increased colonic mucosal eosinophils, which may or may not be associated with inflammatory bowel disease. There is not much clinical data on American children who have isolated increased colonic mucosal eosinophils. We sought to study the clinical correlates of children without inflammatory bowel disease who show increased mucosal eosinophils to understand their clinical presentation, etiological associations, and outcome. A retrospective analysis of children seen at a tertiary-level Children's hospital was performed by reviewing their medical charts and extracting pertinent data. There were 110 children in the study who had increased colonic mucosal eosinophils. Most children presented with abdominal pain, but several of them also had constipation, blood in stools, and diarrhea. Food allergies, irritable bowel syndrome, asthma, and lactase deficiency were the top four conditions present in these patients. Pathology of the colonic distribution revealed involvement of more than two colonic regions in 86% of the subjects, and only two subjects showing epithelial or crypt involvement by eosinophils. All subjects had a good outcome. Children with colonic mucosal eosinophilia (CME) who do not have an inflammatory bowel disease most frequently present with abdominal pain and primarily an increase of lamina propria eosinophils in two or more colonic regions. Based on the etiological associations we noted in the study, a work-up of children with CME may encompass detailed history for functional gastrointestinal disorders and lactose intolerance, testing for food and environmental allergies, stool examination for parasites, and peripheral blood counts. Almost all children had resolution of symptoms in the studied period suggesting that CME in children has a good clinical outcome.

Cytosolic Phosphoenolpyruvate Carboxykinase Deficiency: Cause of Hypoglycemia-Induced Seizure and Death.

Cytosolic phosphoenolpyruvate carboxykinase (PEPCK) deficiency (MIM 261680, EC 4.1.1.32, encoded by PCK1) is a rare disorder of gluconeogenesis presenting with recurrent hypoglycemia, hepatic dysfunction, and lactic acidosis. We report on a previously healthy 3-year-old boy who was initially admitted under the suspicion of a febrile seizure during an upper airway infection. Diagnostic workup revealed hypoglycemia as well as a cerebral edema and ruled out an infection. After a complicated course with difficult to treat symptomatic seizures, the child died on the 5th day of admission due to progressive cerebral edema. The metabolic screening showed elevated urinary lactate and Krebs cycle intermediates in line with a primary or secondary energy deficit. Due to the unclear and fatal course, trio exome sequencing was initiated postmortem ("molecular autopsy") and revealed the diagnosis of cytosolic PEPCK deficiency based on the compound heterozygosity of a known pathogenic (c.925G > A, p.(Gly309Arg)) and a previously unreported (c.724G > A, p.(Gly242Arg)) variant in PCK1 (NM_002591.3). Sanger sequencing ruled out the disease and carrier status in three older brothers. Molecular autopsy was performed due to the unclear and fatal course. The diagnosis of a cytosolic PEPCK deficiency not only helped the family to deal with the grief, but especially took away the fear that the siblings could be affected by an unknown disease in the same manner. In addition, this case increases the genetic and phenotypic spectrum of cytosolic PEPCK deficiency.

A case report of glucose transporter 1 deficiency syndrome with growth hormone deficiency diagnosed before starting ketogenic diet.

BACKGROUND: Growth failure and growth hormone deficiency (GHD) have been reported as one accessory feature of GLUT1 deficiency syndrome (GLUT1DS), considered so far as a long-term adverse effects of ketogenic diet which is used to treat this condition. CASE PRESENTATION: We report the case of a 10-year-old Caucasian boy referred for short stature (height - 2.56 SDS) and delayed growth (growth velocity - 4.33 SDS) who was diagnosed with GHD and started treatment with recombinant human growth hormone (rhGH). Because of his history of seizures with infantile onset, deceleration of head growth with microcephaly, ataxia, and moderate intellectual disability, a lumbar puncture was performed, which revealed a low CSF glucose concentration with a very low CSF-to-blood glucose ratio (< 0.4), and genetic tests detected a SLC2A1 gene exon 1 deletion confirming a diagnosis of GLUT1DS. Ketogenic diet was started. After 5.5 years of rhGH treatment his height was normalized (- 1.15 SDS). No side effects were reported during treatment, particularly on glycemic metabolism. CONCLUSIONS: This is the first case of GHD in a Caucasian boy with GLUT1DS diagnosed before starting ketogenic diet, with a good response to rhGH treatment and absence of side effects. We speculate that GHD may represent a poorly recognized clinical feature of GLUT1DS rather than a complication due to ketogenic diet. Under-diagnosis may derive from the fact that growth failure is usually ascribed to ketogenic diet and therefore not further investigated. Pediatric neurologists need to be alerted to the possible presence of GHD in patients with GLUT1DS with slow growth, while pediatric endocrinologist need to refer GHD patients with additional features (motor and cognitive developmental delay, seizures with infantile onset, deceleration of head growth with acquired microcephaly, movement disorder with ataxia, dystonia, and spasticity) that may suggest GLUT1DS.

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

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.

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.