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)

Pediatric septic thrombosis of intracranial venous sinuses: from diagnosis to discharge. Twenty years of experience. / Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia.

INTRODUCTION: Septic thrombosis of intracranial venous sinuses (STSV) is a rare and severe complication of cranial infections. MATERIALS AND METHODS: The main objective of this paper is to describe the clinical data, diagnostic procedures, treatment and evolution of a series of cases of STSV. In addition, the current literature is reviewed. Observational retrospective study by review of medical histories (January 1995-December 2016). The data collected were: clinical, analytical, epidemiological, microbiological, radiological, management and follow-up. A descriptive and statistical analysis of the data was done. RESULTS: Twelve children were included (86,832 admissions studied). They have a median age of 4.5 years (range 1-13) with a median time of symptoms of 6 days (range 1-25). At admission, the clinical data were: fever (11/12), vomiting (9/12) and headache (8/12). They also showed bad general status 12/12, 7/12 acute otitis media and 5/12 VI cranial nerve paresis. The lumbar puncture was pathological in 4/12. The most frequently microorganism isolated was Streptococcus sp. Prothrombotic mutations were confirmed on 2/12. Cranial computed tomography allowed diagnosis in 9/12; the magnetic resonance imaging achieves that in 12/12. Previous neurological signs or time to diagnosis did not influence the appearance of other image complications. All received antibiotic treatment, heparin 10/12 and 11/12 surgery. There were no sequels. CONCLUSION: In our series otitis, headache, vomiting and fever were prevalent. Complementary tests allowed the suspect but the definitive diagnosis was obtained by neuroimaging. There were no sequels and the therapies were mainly wide broad-spectrum antibiotics, heparin, and surgical.

TITLE: Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia.Introducción. La trombosis séptica de los senos venosos intracraneales (TSSV) es una complicación rara y grave de las infecciones craneales. Materiales y métodos. El objetivo principal de este trabajo es describir los datos clínicos, procedimientos diagnósticos, tratamiento y evolución de una serie de casos de TSSV. Además, se revisa la bibliografía actual. Es un estudio retrospectivo observacional mediante revisión de historias médicas (enero de 1995-diciembre de 2016). Los datos recogidos fueron: clínicos, analíticos, epidemiológicos, microbiológicos, radiológicos, de manejo y de seguimiento. Se realizó un análisis descriptivo y estadístico de los datos. Resultados. Se incluyó a 12 niños (86.832 ingresos estudiados). La mediana de edad fue de 4,5 años (rango: 1-13), con un tiempo medio de síntomas de 6 días (rango: 1-25). En el momento de la admisión, los datos clínicos fueron: fiebre (11/12), vómitos (9/12) y dolor de cabeza (8/12). También mostraron mal estado general, 12/12; otitis media aguda, 7/12; y paresia del VI par craneal, 5/12. La punción lumbar fue patológica en 4/12. El microorganismo más frecuentemente aislado fue Streptococcus spp. Se confirmaron mutaciones protrombóticas en 2/12. La tomografía computarizada craneal permitió el diagnóstico en 9/12; la resonancia magnética lo logró en 12/12. Los signos neurológicos anteriores o el tiempo de diagnóstico no influyeron en la aparición de otras complicaciones de la imagen. Recibieron tratamiento antibiótico 12/12; heparina, 10/12; y cirugía, 11/12. No hubo secuelas. Conclusión. En nuestra serie, la otitis, el dolor de cabeza, los vómitos y la fiebre fueron frecuentes. Las pruebas complementarias permitieron el diagnóstico de sospecha, pero el diagnóstico definitivo se obtuvo por neuroimagen. No hubo secuelas y las terapias fueron principalmente antibióticos de amplio espectro, heparina y cirugía.

Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia / Pediatric septic thrombosis of intracranial venous sinuses: from diagnosis to discharge. Twenty years of experience

Introducción: La trombosis séptica de los senos venosos intracraneales (TSSV) es una complicación rara y grave de las infecciones craneales. Materiales y métodos: El objetivo principal de este trabajo es describir los datos clínicos, procedimientos diagnósticos, tratamiento y evolución de una serie de casos de TSSV. Además, se revisa la bibliografía actual. Es un estudio retrospectivo observacional mediante revisión de historias médicas (enero de 1995-diciembre de 2016). Los datos recogidos fueron: clínicos, analíticos, epidemiológicos, microbiológicos, radiológicos, de manejo y de seguimiento. Se realizó un análisis descriptivo y estadístico de los datos. Resultados: Se incluyó a 12 niños (86.832 ingresos estudiados). La mediana de edad fue de 4,5 años (rango: 1-13), con un tiempo medio de síntomas de 6 días (rango: 1-25). En el momento de la admisión, los datos clínicos fueron: fiebre (11/12), vómitos (9/12) y dolor de cabeza (8/12). También mostraron mal estado general, 12/12; otitis media aguda, 7/12; y paresia del VI par craneal, 5/12. La punción lumbar fue patológica en 4/12. El microorganismo más frecuentemente aislado fue Streptococcus spp. Se confirmaron mutaciones protrombóticas en 2/12. La tomografía computarizada craneal permitió el diagnóstico en 9/12; la resonancia magnética lo logró en 12/12. Los signos neurológicos anteriores o el tiempo de diagnóstico no influyeron en la aparición de otras complicaciones de la imagen. Recibieron tratamiento antibiótico 12/12; heparina, 10/12; y cirugía, 11/12. No hubo secuelas. Conclusión: En nuestra serie, la otitis, el dolor de cabeza, los vómitos y la fiebre fueron frecuentes. Las pruebas complementarias permitieron el diagnóstico de sospecha, pero el diagnóstico definitivo se obtuvo por neuroimagen. No hubo secuelas y las terapias fueron principalmente antibióticos de amplio espectro, heparina y cirugía.(AU)

Introduction: Septic thrombosis of intracranial venous sinuses (STSV) is a rare and severe complication of cranial infections. Materials and methods: The main objective of this paper is to describe the clinical data, diagnostic procedures, treatment and evolution of a series of cases of STSV. In addition, the current literature is reviewed. Observational retrospective study by review of medical histories (January 1995-December 2016). The data collected were: clinical, analytical, epidemiological, microbiological, radiological, management and follow-up. A descriptive and statistical analysis of the data was done. Results: Twelve children were included (86,832 admissions studied). They have a median age of 4.5 years (range 1-13) with a median time of symptoms of 6 days (range 1-25). At admission, the clinical data were: fever (11/12), vomiting (9/12) and headache (8/12). They also showed bad general status 12/12, 7/12 acute otitis media and 5/12 VI cranial nerve paresis. The lumbar puncture was pathological in 4/12. The most frequently microorganism isolated was Streptococcus sp. Prothrombotic mutations were confirmed on 2/12. Cranial computed tomography allowed diagnosis in 9/12; the magnetic resonance imaging achieves that in 12/12. Previous neurological signs or time to diagnosis did not influence the appearance of other image complications. All received antibiotic treatment, heparin 10/12 and 11/12 surgery. There were no sequels. Conclusion: In our series otitis, headache, vomiting and fever were prevalent. Complementary tests allowed the suspect but the definitive diagnosis was obtained by neuroimaging. There were no sequels and the therapies were mainly wide broad-spectrum antibiotics, heparin, and surgical.(AU)

Neonato con sobreinfección de un cefalohematoma complicado con meningitis: a propósito de un caso / Newborn with infected cephalohematoma complicated with meningitis: report of one case

INTRODUCCIÓN: La infección del cefalohematoma es una patología muy infrecuente, aunque potencialmente grave por las complicaciones asociadas que puede conllevar: osteomielitis del hueso subyacente, meningitis o sepsis. CASO CLÍNICO: Se expone un caso de una recién nacida por cesárea con antecedente de atresia duodenal intervenida, que desarrolla, al octavo día de vida, la infección de un cefalohematoma con cuadro séptico y meningitis asociada. Tras un drenaje del cefalohematoma y la administración de antibioterapia durante 3 semanas, la paciente evoluciona favorablemente. CONCLUSIÓN: Ante la sospecha de la infección de un cefalohematoma, el drenaje del mismo es la clave diagnóstica y terapéutica, ya que la antibioterapia de forma aislada puede no ser suficiente para erradicar el patógeno. Se deben descartar otras complicaciones asociadas, como meningitis, sepsis u osteomielitis del hueso subyacente

INTRODUCTION: The infection of a cephalohematoma is an infrequente but potentially fatal condition due to its possible complications such as osteomyelitis, meningitis or sepsis. CASE REPORT: The report describes a newborn delivered by cesarean section, and a history of duodenal atresia with surgical correction, who develops, at 8 days of life, an infection of a cephalohematoma with sepsis and meningitis. After aspiration of the cephalohematoma and a three week course of antibiotics, she showed a favorable outcome. CONCLUSION: When the infection of a cephalohematoma is suspected, its drainage is both a diagnostic and therapeutic tool, as antibiotic therapy alone is often insufficient. Possible complications such as meningitis, osteomyelitis and sepsis must be ruled out

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

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.