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.

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.

Genetic and phenotypic analysis of a patient with phosphogylcerate dehydrogenase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with ocular anomaly, microcephaly, growth retardation and intrauterine growth restriction.@*METHODS@#The patient underwent ophthalmologic examinations including anterior segment photography, fundus color photography, and fundus fluorescein angiography. The patient and her parents were subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The patient was found to have bilateral persistent pupillary membrane and coloboma of inferior iris, in addition with macular dysplasia and radial pigmentation near the hemal arch of the temporal retina. She was found to have carried compound heterozygous missense variants of the PHGDH gene, namely c.196G>A and c.1177G>A, which were respectively inherited from her father and mother. Bioinformatic analysis suggested both variants to be pathogenic.@*CONCLUSION@#The patient was diagnosed with phosphoglycerate dehydrogenase deficiency. Above finding has enriched the phenotypic spectrum of the disease with ocular manifestations.

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.

Karyotyping and population genetics in Cold War Mexico: Armendares's and Lisker's characterization of child and indigenous populations, 1960s-1980s / Cariotipia e genética de populações no México da Guerra Fria: as caracterizações de Armendares e Lisker sobre as populações infantil e indígena, 1960-1980

Abstract This paper focuses on geneticists Salvador Armendares's and Rubén Lisker's studies from the 1960s to the 1980s, to explore how their work fits into the post-1945 human biological studies, and also how the populations they studied, child and indigenous, can be considered laboratories of knowledge production. This paper describes how populations were considered for different purposes: scientific inquiry, standardization of medical practices, and production or application of medicines. Through the narrative of the different trajectories and collaborations between Armendares and Lisker, this paper also attempts to show the contact of their scientific practices, which brought cytogenetics and population genetics together at the local and global levels from a transnational perspective.

Resumo Aborda o trabalho dos geneticistas Salvador Armendares e Rubén Lisker, entre 1960 e 1980, para analisar como se insere nos estudos biológicos humanos do pós-1945, e demonstra como as populações estudadas por eles, a infantil e a indígena, podem ser consideradas laboratórios de produção de conhecimento. O artigo revela como as populações foram consideradas para diversos propósitos: investigação científica, padronização das práticas médicas e produção ou aplicação de suas medicinas. Por meio da narrativa das diferentes trajetórias e colaborações entre Armendares e Lisker, também procura discutir o contato de suas práticas científicas, que colocaram a citogenética e a genética de populações lado a lado nos níveis local e global a partir de uma perspectiva transnacional.

Glucose transporter 1 deficiency syndrome: features of movement disorders, diagnosis and treatment / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical features, diagnosis and treatment of glucose transporter 1 deficiency syndrome (GLUT1-DS), as well as the diagnostic value of movement disorders.</p><p><b>METHODS</b>The clinical data of four children with GLUT1-DS were collected, and their clinical features, treatment, and follow-up results were analyzed.</p><p><b>RESULTS</b>There were two boys and two girls, with an age of onset of 2-15 months. Clinical manifestations included movement disorders, seizures, and developmental retardation. Seizures were the cause of the first consultation in all cases. The four children all had persistent ataxia, dystonia, and dysarthria; two had persistent tremor, two had paroxysmal limb paralysis, and two had eye movement disorders. Paroxysmal symptoms tended to occur in fatigue state. All four children had reductions in the level of cerebrospinal fluid glucose and its ratio to blood glucose, as well as SLC2A1 gene mutations. The four children were given a ketogenic diet, at a ketogenic ratio of 2:1 to 3:1, and achieved complete remission of paroxysmal symptoms within 5 weeks.</p><p><b>CONCLUSIONS</b>GLUT1-DS should be considered for epileptic children with mental retardation and motor developmental delay complicated by various types of movement disorders. The ketogenic diet is effective at a ketogenic ratio of 2:1 to 3:1 for the treatment of GLUT1-DS.</p>

Clinical and genetic characteristics of glucose transporter type 1 deficiency syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the clinical and SLC2A1 gene mutation characteristics of glucose transporter type 1 deficiency syndrome.</p><p><b>METHOD</b>The detailed clinical manifestations of six cases were recorded. The laboratory tests including EEG, MRI, blood chemistry, and lumbar puncture were performed. SLC2A1 gene mutations were analyzed by PCR, DNA sequencing and multiplex ligation-dependent probe amplification (MLPA).</p><p><b>RESULT</b>Patient 1, 2 and 3 had classical clinical symptoms including infantile onset seizures, development delay. Patient 4, 5 and 6 had non-classical clinical symptoms including paroxysmal behavior disturbance, weakness, ataxia, lethargy, especially after fasting or exercise, without severe seizures. The plasma glucose levels were normal. The CSF glucose levels decreased in all the six cases, ranged from 1.10 mmol/L to 2.45 mmol/L, the mean level was 1.68 mmol/L. The CSF glucose/plasma glucose ratios decreased, ranged from 0.16 to 0.51, the mean ratio was 0.34. Four patients had normal EEG. Two patients had focal and diffuse epileptiform discharge, and one of them also had paroxysmal occipital or generalized high-amplitude slow waves during awake and sleep time. MRI abnormalities were found in three patients, patient 1 with mild brain atrophy, patient 3 with bilateral ventricle plump, and patient 4 with high signals in T2 in the frontal and occipital white matter, interpreted as hypomyelination. SLC2A1 gene mutations were found in six cases. Patient 1 has large scale deletion in exon 2. In patient 2 to 6, the mutations were c.741 G>A (E247K), 599delA, 761delA, c.1148 C>A (P383H), c.1198 C>T (R400C) respectively. Two patients were treated with ketogenic diet. The seizures disappeared and development became normal. Three patients responded to frequent meals with snacks. One patient refused any treatments, the symptoms continued to exist.</p><p><b>CONCLUSION</b>The clinical manifestations of glucose transporter type 1 deficiency syndrome are varied. The common symptoms included infantile onset seizures and various paroxysmal events. These neurologic symptoms generally fluctuated and were influenced by factors such as fasting or fatigue. This feature could be a very important clue for the diagnosis of GLUT1-DS. Lumbar puncture is recommended in patients with episodic CNS symptoms especially after fasting. GLUT1-DS is a treatable neurometabolic disorder, early diagnosis and treatment may improve the prognosis of the patients.</p>

Síndrome de deficiencia del transportador de glucosa tipo 1 (SDGLUT-1) tratado con dieta cetogénica: Caso clínico / Glucose transponer type 7 deficiency síndrome (GLUT-1 SD) treated with ketogenic diet: Report of one case

The glucose transporter type 1 deficiency syndrome (GLUT-1 SD) (OMIM 606777) is an inborn error of metabolism of brain glucose transport. The characteristic clinical manifestations are seizures, hypotonia, developmental delay, microcephaly and hypoglycorrhachia. We report a girl with normal weight and height at birth. At 6 weeks of age she started with convulsions reaching up to 20 myoclonic seizures a day. She was treated with valproate, phenobarbital and carbamazepine without response. Blood analysis including aminoacids and acylcarnitines were all normal. The brain MRI showed frontal atrophy with an increased subarachnoidal space and Electroencephalography was abnormal. Blood glucose was 84 mg/dl and spinal fluid glucose 26 mg/dl with a ratio of 0.31 (Normal Ratio >0.65+00.1). These results suggested the diagnosis of GLUT-1 SD, and was confirmed with erythrocyte glucose uptake of 44 percent (Normal range 80-100 percent). A molecular study found the mutation 969del, C971T in exon 6 of the gene Glut-1. Treatment with a ketogenic diet was started immediately and after 7 days with this diet seizures ceased. Anticonvulsants were progressively suspended. At present, the patient is 6 years old, she continues on a ketogenic diet and supplements with L-carnitine, lipoic acid, vitamins and minerals. Growth and development are normal with an intelligence quotient of 103. It is concluded that it is necessary to include GLUT-1 SD in the differential diagnosis of children with early seizures that are non responsive to pharmacological treatment.

Inborn errors of amino acid and carbohydrate metabolism

This study was conducted with two objects in mind. Firstly, to screen children who were under two years of age for detection of inborn errors of Amino Acid and Carbohydrate metabolism. Secondly, a group of cases of proved mental deficiency were screened to find out whether the inborn errors of Amino Acid and Carbohydrate metabolism are a significant contributory factor to the mental deficiency in Pakistan. Department of Pathology, PGMI/ KEMC/ Mayo Hospital Lahore. In this study, two groups of subjects were investigated systematically to detect inborn errors of amino acid and carbohydrate metabolism with particular reference to Alcaptonuria, Phenylketonuria, Galactosemia, FruSosuria and pentosuria. In group I - 2000 children, under 2 years of age, mostly newborns, were randomly selected for this study from Pediatrics department of various hospitals of Lahore. Group II - Includes 30 cases of mental deficiency of various ages referred by the psychiatrists or pediatricians for verifying whether any inborn error of Amino Acid or Carbohydrates metabolism is present or not. Chemical screening tests along with one dimensional descending paper chromatography and thin layer chromatography [TLC] were employed to detect metabolic errors. In group I, one case of alcaptonuria was detected In group II, Three cases of a specific generalized aminoaciduria occurring in a single family were detected. This study indicates that inborn errors of metabolism also exist in Pakistan. It has also sorted out a reliable scheme of screening and detection of these disorders suited to our socio-economic.environment. The importance of early suspicion of these disorders and a timely diagnosis during preventable stage has been stressed and the need of a national screening programme highlighted

Alteraciones del metabolismo de los carbohidratos generadas por el uso de antirretrovirales en pacientes con SIDA / Altered carbohydrate metabolism in AIDS patients under antiretrovirals

La incorporación de los inhibidores de proteasas (IPs) al tratamiento antirre t roviral de gran actividad (TA R G A )ha mejorado rápidamente tanto el curso de la enfermedad como la morbi-mortalidad y la expectativa de vida de los pacientes con infección por HIV/ SIDA. Sin embargo, algunas evidencias indican que la exposición a los IP podríaimplicar el riesgo de desarrollar trastornos metabólicos tales como atero sclerosis, lipodistrofias, dislipemias y diabetes insulin o - resistente. En este trabajo se revisan los aspectos epidemiológicos, las implicancias, los mecanismos celulares y los aspectos de relevancia clínica para el manejo y control de las alteraciones metabólicas de los hidratos de carbono relacionadas con los antirretrovirales.

Incidence and risk factors for carbohydrate intolerance in Thai infants with acute diarrhea: an outpatient-based study.

Until recently, information concerning carbohydrate intolerance complicating acute infantile diarrhea of outpatients in Thailand has been lacking. This prospective study was undertaken to determine the incidence and risk factors of secondary carbohydrate intolerance in outpatients. Of 197 well-nourished infants with acute diarrhea who were seen at the outpatient department of Songklanagarind Hospital between July 1991 and June 1992, 62 infants (31.3%) had carbohydrate intolerance, and 7 of the 62 (3.5%) also had acquired monosaccharide intolerance. The clinical characteristics that predicted infants with carbohydrate intolerance were : a low bodyweight relative to the length, dehydration (OR 4.55, 95% CI 1.1.5-17.9), the presence of mucus in diarrheal stools (OR 2.79, 95% CI 1.23-6.32) and rotavirus infection (OR 3.49, 95% CI 1.20-10.18).

Indice glucémico de algunos alimentos comunes en México / Glycemic index of some foods common in the mexican diet

Para investigar la magnitud de la glucemia por ingerir algunos alimentos comunes en México, el índice glucémico se determinó en 21 individuos sanos y 27 diabéticos no dependientes de insulina después de comer tortilla de maíz blanco y de maíz amarillo, espagueti, arroz, papa, frijol bayo o negro, nopal y cacahuate, comparado con el alcanzado con pan blanco. Para ello se administraron porciones con 50 g de carbohidratos y la glucemia se midió cada 30 minutos durante tres horas. El índice glucémico se calculó como: (área bajo la curva con el alimento de prueba/área bajo la curva con pan) X100. Para valorar las modificaciones debidas exclusivamente al alimento se obtuvo un índice corregido restando el área correspondiente a la cifra basal. En la misma forma se calcularon índices insulínicos. Cada muestra se estudió de 14 a 18 veces. Se encontró que los índices glucémicos e insulínicos con tortilla blanca y amarilla, espagueti, arroz y papa son similares a los obtenidos con pan (p>0.05); los índices glucémicos corregidos con frijol bayo (54+-15)(X+-ES) y frijol negro (43+-17) fueron moderadamente bajos (P<0.05) al igual que el índice insulínico corregido (69+-11 y 64+-10 respectivamente, P<0.02). Con cacahuate el índice glucémico estuvo bajo (33+-17,P<0.01), más no el insulínico. Con nopal ambos índices corregidos resultaron muy bajos (glucémico 10+-17, insulínico 10+-16, P<0.0001). Estos resultados pueden ser útiles para formular dietas para pacientes con diabetes mellitus

Dosagem de ácido siálico urinário em crianças normais e sua aplicaçäo para a determinaçäo de sialidoses e sialúrias / Urinary sialic acid measurement in normal childrens and it application in sialidosis and sialuria determination

A determinaçäo do ácido siálico urina é um método útil para a detecçäo de diversas doenças genéticas nas quais há um distúrbio no metabolismo desse composto, denominadas "sialidoses" (incluindo sialidose e galactosialidose) "sialúrias" (incluindo doenças de Salla e doença infantil de acúmulo de ácido siálico). Neste trabalho foram determinadas as concentraçöes urinárias de ácido siálico em 43 crianças normais, cujas idades variaram de 6 meses a 8 anos e meio. Foram estabelecidos os níveis normais para a concentraçäo urinária de ácido siálico livre e total, os quais declinaram sensivelmente com o aumento da idade. A medida da fraçäo livre é recomendada uma vez que seu aumento ocorre nas sialúrias, enquanto que nas sialidoses o que ocorre é um aumento da fraçäo ligada. Os dados apresentados säo importantes para a interpretaçäo dos resultados da dosagem de ácido siálico urinário em crianças, tendo sua utilidade sido comprovada pela avaliaçäo de dois casos de sialidose previamente diagnosticados

relation between chronic gall bladder diseases and disturbed carbohydrate metabolism

The relation between pancreaticobiliary disorders and diabetes mellitus was studied in 20 patients with chronic gallbladder disorders, 13 of them were less obese non-diabetics and 10 healthy individuals. They were subjected to plain X-ray and cholecystogram, blood sugar and blood lipids estimation, liver function tests and endocrine as well as exocrine pancreatic function tests