RESUMO
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.
Assuntos
Humanos , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/terapia , Proteínas de Transporte de Monossacarídeos/genética , Epilepsia/diagnóstico , Epilepsia/genética , MutaçãoRESUMO
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.
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.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos , Humanos , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/genética , Erros Inatos do Metabolismo dos Carboidratos/terapia , Epilepsia/diagnóstico , Epilepsia/genética , Proteínas de Transporte de Monossacarídeos/genética , MutaçãoRESUMO
OBJECTIVE: To profile the initial clinical events of glucose transporter 1 deficiency syndrome (Glut1 DS) in order to facilitate the earliest possible diagnosis. STUDY DESIGN: We retrospectively reviewed 133 patients with Glut1 DS from a single institution. Family interviews and medical record reviews identified the first clinical event(s) reported by the caregivers. RESULTS: Average age of the first event was 8.15 ± 11.9 months (range: 0.01-81). Ninety-one patients experienced the first symptom before age 6 months (68%). Thirty-three additional patients (25%) presented before age 2 years. Only 9 patients (7%), reported the first event after age 2 years. Seizures were the most common first event (n = 81, 61%), followed by eye movement abnormalities (n = 51, 38%) and changes in muscle strength and tone (n = 30, 22%). Eye movement abnormalities, lower cerebrospinal fluid glucose values, and lower Columbia Neurological Scores correlated with earlier onset of the first event (r: -0.17, 0.22, and 0.25 respectively, P < .05). There was no correlation with age of first event and red blood cell glucose uptake or mutation type. CONCLUSIONS: Glut1 DS is a treatable cause of infantile onset encephalopathy. Health care providers should recognize the wide spectrum of paroxysmal events that herald the clinical onset of Glut1 DS in early infancy to facilitate prompt diagnosis, immediate treatment, and improved long-term outcome.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Transportador de Glucose Tipo 1/deficiência , Idade de Início , Anticonvulsivantes/uso terapêutico , Encéfalo/crescimento & desenvolvimento , Erros Inatos do Metabolismo dos Carboidratos/terapia , Cuidadores , Criança , Pré-Escolar , Dieta Cetogênica , Intervenção Médica Precoce , Epilepsia/diagnóstico , Movimentos Oculares , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prontuários Médicos , Pediatria/métodos , Estudos Retrospectivos , Convulsões/diagnóstico , Convulsões/tratamento farmacológicoAssuntos
Erros Inatos do Metabolismo dos Carboidratos/genética , Fenótipo , Complexo Sacarase-Isomaltase/deficiência , Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/terapia , Diarreia Infantil/etiologia , Diarreia Infantil/terapia , Glicosídeo Hidrolases/administração & dosagem , Humanos , Lactente , Alimentos Infantis/efeitos adversos , Saccharomyces cerevisiae/enzimologia , beta-FrutofuranosidaseRESUMO
Blood galactose concentrations were measured in 55 neonates consuming at least 80 ml/kg/day of lactose-containing formula. The range of galactose concentration immediately after feeding was 0.8 to 4.2 mg/dl, with a mean of 1.5 +/- 0.2 mg/dl. Galactose concentration fell rapidly after feeding, and normal values for the population fell with a half-life of 45 minutes. Considering galactose as a potential intravenous nutrient, six glucose-intolerant premature infants were given galactose-containing solutions intravenously using a double-blind randomized crossover protocol. Infants were chosen who had sustained hyperglycemia (150 mg/dl) and glucosuria (2+ Clinitest) requiring glucose infusion at a rate below 7 mg/kg/minute for more than 24 hours. Compared to the control glucose period, intravenous alimentation with a solution containing carbohydrate as 50% glucose and 50% galactose resulted in a 65% increase in total carbohydrate infusion rate, normalization of the blood glucose concentration, and decreased glucosuria. Blood galactose concentration averaged 15 mg/dl, and no clinical or biochemical evidence of galactose toxicity was noted.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/terapia , Galactose/administração & dosagem , Doenças do Prematuro/terapia , Infusões Parenterais/métodos , Glicemia/análise , Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Ensaios Clínicos como Assunto , Método Duplo-Cego , Galactose/metabolismo , Galactosemias , Glucose/administração & dosagem , Glucose/metabolismo , Glicosúria , Humanos , Recém-Nascido , Doenças do Prematuro/metabolismo , Fígado/metabolismo , Distribuição AleatóriaRESUMO
The study in 14 patients with severe and protracted infectious gastroenteritis is reported. In all cases, intolerance to monosaccharides was present and in 13 cases, third degree malnutrition was evident. The period of evolution of the diarrhea was, as an average, 67.6 days at the moment when parenteral feeding was initiated. Eight of the cases had shown sepsis, intestinal pneumatosis and hypoglycemia in six and gastrointestinal hemorrhage was found in another six patients. They were managed with parenteral feeding for an average period of 21.5 days, during which, they gained an average of 14.6 g/day. Six episodes of sepsis were seen during the procedure, but in no case did it follow infection through the central catheter. Four of the patients died, but in no case was there any direct relationship to the procedure. In this type of severely ill patients with protracted diarrhea, parenteral feeding is a resource that allows the defunctionalization of the intestine and recovery of these patients.