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Glutaric aciduria type I is a rare disorder of organic acid metabolism caused by deficiency of glutaryl-CoA dehydrogenase, a mitochondrial enzyme. Improper degeneration of amino acids: tryptophan, lysine, and hydroxylysine, results in increased levels of glutaric acid, which typically becomes clinically manifest as an acute dystonic crisis in young children. Accumulation of glutaric acid causes neurotoxicity in the basal ganglia and fronto-temporal cortex which can lead to progressive dystonia, hypotonia, permanently impaired speech and seizures. Because dietary and drug therapy may alter the natural history of the disease, early diagnosis of such patients is critical. We report the magnetic resonance (MR) imaging findings in a 16 year-old girl with this disorder who presented with a chronic dystonic syndrome and previously diagnosed of brain paralysis. MR imaging demonstrated bilateral involvement of the putamina and periventricular white matter, and bilateral temporal atrophy and widened Silvian fissures

WOS: 000481590200024, PubMed ID: 31427717, Rett syndrome (RTT) is a severe neurological disorder usually caused by mutations in the MECP2 gene. Since the MECP2 gene is located on the X chromosome, X chromosome inactivation (XCI) could play a role in the wide range of phenotypic variation of RTT patients; however, classical methylation-based protocols to evaluate XCI could not determine whether the preferentially inactivated X chromosome carried the mutant or the wild-type allele. Therefore, we developed an allele-specific methylation-based assay to evaluate methylation at the loci of several recurrent MECP2 mutations. We analyzed the XCI patterns in the blood of 174 RTT patients, but we did not find a clear correlation between XCI and the clinical presentation. We also compared XCI in blood and brain cortex samples of two patients and found differences between XCI patterns in these tissues. However, RTT mainly being a neurological disease complicates the establishment of a correlation between the XCI in blood and the clinical presentation of the patients. Furthermore, we analyzed MECP2 transcript levels and found differences from the expected levels according to XCI. Many factors other than XCI could affect the RTT phenotype, which in combination could influence the clinical presentation of RTT patients to a greater extent than slight variations in the XCI pattern., Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER) [PI15/01159]; Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); Catalan Association for Rett Syndrome; Fondobiorett; Mi Princesa Rett, We thank all patients and their families who contributed to this study. The work was supported by grants from the Spanish Ministry of Health (Instituto de Salud Carlos III/FEDER, PI15/01159); Crowdfunding program PRECIPITA, from the Spanish Ministry of Health (Fundacion Espanola para la Ciencia y la Tecnologia); the Catalan Association for Rett Syndrome; Fondobiorett and Mi Princesa Rett.

Rett syndrome (RTT) is an early-onset neurodevelopmental disorder that almost exclusively affects girls and is totally disabling. Three genes have been identified that cause RTT: MECP2, CDKL5 and FOXG1. However, the etiology of some of RTT patients still remains unknown. Recently, next generation sequencing (NGS) has promoted genetic diagnoses because of the quickness and affordability of the method. To evaluate the usefulness of NGS in genetic diagnosis, we present the genetic study of RTT-like patients using different techniques based on this technology. We studied 1577 patients with RTT-like clinical diagnoses and reviewed patients who were previously studied and thought to have RTT genes by Sanger sequencing. Genetically, 477 of 1577 patients with a RTT-like suspicion have been diagnosed. Positive results were found in 30% by Sanger sequencing, 23% with a custom panel, 24% with a commercial panel and 32% with whole exome sequencing. A genetic study using NGS allows the study of a larger number of genes associated with RTT-like symptoms simultaneously, providing genetic study of a wider group of patients as well as significantly reducing the response time and cost of the study.

OBJECTIVES: To study the relationship between behavioural profile of children suffering from Attention Deficit Hyperactivity Disorder (ADHD) and the previous behavioural style of these patients as toddlers. SUBJECTS AND METHODS: We asked the parents of 50 schoolchildren with ADHD, and those of 30 controls, to fill in a Spanish version of the Toddler Behaviour Questionnaire (TBQ) from their retrospective perception of their children's behaviour as toddlers. TBQ items were grouped by factor analysis; t-Student between the scores of both groups and a multiple correlation analysis of TBQ and DSM-IV-ADHD-RS in each of the groups were used. RESULTS: Children in the ADHD group were reported by parents to have had a different toddler behavioural profile in comparison to that of control children (P

The main disabilities in non-verbal learning disorder (NLD) are: the acquisition and automating of motor and cognitive processes, visual spatial integration, motor coordination, executive functions, difficulty in comprehension of the context, and social skills. AIMS. To review the research to date on NLD, and to discuss whether the term 'procedural learning disorder' (PLD) would be more suitable to refer to NLD. DEVELOPMENT: A considerable amount of research suggests a neurological correlate of PLD with dysfunctions in the 'posterior' attention system, or the right hemisphere, or the cerebellum. Even if it is said to be difficult the delimitation between NLD and other disorders or syndromes like Asperger syndrome, certain characteristics contribute to differential diagnosis. Intervention strategies for the PLD must lead to the development of motor automatisms and problem solving strategies, including social skills. CONCLUSIONS: The basic dysfunction in NLD affects to implicit learning of routines, automating of motor skills and cognitive strategies that spare conscious resources in daily behaviours. These limitations are partly due to a dysfunction in non-declarative procedural memory. Various dimensions of language are also involved: context comprehension, processing of the spatial and emotional indicators of verbal language, language inferences, prosody, organization of the inner speech, use of language and non-verbal communication; this is why the diagnostic label 'PLD' would be more appropriate, avoiding the euphemistic adjective 'non-verbal'.

Epilepsia. 2007 Sep;48(9):1678-85. Epub 2007 Jun 11. Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. Marini C, Mei D, Temudo T, Ferrari AR, Buti D, Dravet C, Dias AI, Moreira A, Calado E, Seri S, Neville B, Narbona J, Reid E, Michelucci R, Sicca F, Cross HJ, Guerrini R. SourceEpilepsy, Neurophysiology and Neurogenetic Unit, Institute of Child Neurology and Psychiatry, IRCCS Stella Maris Foundation, Calambrone, Pisa, Italy. Abstract PURPOSE: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. METHODS: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. RESULTS: We classified patients as: SMEI/SMEB = 55; GEFS+= 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. CONCLUSION: We obtained a frequency of 71%SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes.

Purpose: Mutations in the genes coding for subunits of ion channels have been associated with epilepsy. Of these known epilepsy genes SCN1A, coding for the α subunit of the sodium channel, is currently the most clinically relevant gene. The majority of SCN1A mutations lead to severe myoclonic epilepsy of infancy (SMEI) including borderline SMEI (SMEB) and to generalized epilepsy with febrile seizures plus (GEFS+). Both syndromes have febrile seizures (FS) as a common clinical feature. The aim of this study was to achieve a better definition of the spectrum of phenotypes that might be associated with SCN1A mutations. We aimed to performing phenotype-genotype correlations of SCN1A mutations with specific epilepsy syndromes. Methods: We selected 132 patients in whom most seizures occurred during febrile episodes. A clinical and genetic study focussing on SCN1A screening was performed. Results: Patients were classified as follow: SMEI/ SMEB = 55; GEFS+ spectrum= 25; sporadic myoclonic astatic epilepsy= 3; classical FS= 10; other phenotypes= 25. We identified 40 SCN1A mutations. Of the 40 mutations 37 were found in patients with SMEI in whom mutations were missense in 16 probands (2 familial) and truncating in 21 (2 familial). The remaining 3 missense mutations were associated with GEFS+. Missense mutations in the pore forming parts (S5-S6) of the Na+ channel occurred in 10 out of the 16 SMEI (62,5%) and only in one of the three GEFS+ patients. Mutations in the pore forming region seem to correlate in 70% with the classical SMEI type and only with 30% of the SMEB phenotype. Analysis of the age of seizures onset between SMEI patients with: a) SCN1A truncating mutations, b) SCN1A missense mutations and c) no SCN1A mutations showed that the differences of the age of FS onset was extremely significant between the three groups (p=0,0007, ANOVA test). Patients with truncating mutations had the earlier onset of FS, patients with missense mutations had an intermediate onset, and individuals without SCN1A mutations had the latest age of FS onset. Conclusion: We obtained a prevalence of about 70% of SCN1A mutations in SMEI and SMEB patients and of 12% in GEFS+ probands confirming the predominant and important role of SCN1A in patients with SMEI. None of the other patients with fever-provoked seizures carried mutations in SCN1A gene. The high correlation between SMEI and SCN1A mutations suggests a phenotypical specificity of SCN1A rather than a dysfunction of neurons exacerbated by high body temperature

La visión suministra una perspectiva global, simultánea y anticipadora del entorno. Un déficit severo de visión constituye un obstáculo para el adecuado desarrollo cognitivo y social del niño. La respuesta educativa a las necesidades prioritarias que la deficiencia visual genera, requiere una adecuada formación por parte de los profesionales: Para ello, es preciso que adquieran los conocimientos básicos relativos a la clasificación y el diagnóstico de la deficiencia visual, los aspectos esenciales del desarrollo y los fundamentos de la intervención educativa. El objetivo del presente trabajo es analizar las principales características de la deficiencia visual en los niños, y el impacto que dicha deficiencia tiene en el desarrollo y en el aprendizaje.

Introducción y objetivos. Resultados positivos en el tratamiento de la parálisis cerebral infantil espástica con toxina botulínica, en estudios anglosajones de los últimos años, nos han llevado a iniciar este trabajo, cuyo objetivo es mostrar nuestra experiencia con la toxina en el tratamiento de esta enfermedad, establecer sus indicaciones, analizar los resultados obtenidos y plantear posibles aplicaciones futuras. Material y métodos. Incluimos 10 pacientes hemipléficos y 17 dipléjicos de edad media 6 años y 7 meses, seguidos entre 5 y 18 meses. Aplicamos PRS y EVFEL como escalas de valoración y medimos el rango de movilidad articular seis meses antes de infiltrar la toxina, y en el seguimiento tras su aplicación y prosecución de fisioterapia. Infiltramos adductores, isquiotibial interno, tríceps sural y tibial posterior, en dosis de 1 - 2 U/músculo/kg de peso corporal. Resultados. Encontramos mejoría media en PRS del 24%, el ángulo de adductores mejoró un 66% (p

La incidencia del absceso cerebral en edad pediátrica es muy baja, a pesar de lo cual s una patología importante por las frecuentes y graves consecuencias que puede comportar. Las infecciones otorrinolaringológicas y las meningoencefalitis son su principal origen, así como las cardiopatías congénitas cianosantes.

El amplio capítulo de las "disfasias o afasias del desarrollo" y el síndrome de "afasia infantil adquirida y persistente con comicialidad", son ocasión de estudio de modelos clínicos neuro-lingüísticos en los cuales se alteran y recuperan las funciones de decoficiación y codificación verbal en el cerebro en desarrollo . Dos pacientes ejemplifican cada una de las situaciones cita- das.

Los autores comunican la observación de una familia en la que tres miembros de 2 generaciones han presentado crisis convulsivas durante el periodo neonatal sin causa central ni metabólica demostrable, con evolución psicomotriz ulterior normal. Hasta el presente se han publicado otras siete familias con un cuadro superponible. Se discuten las características del síndrome.

Las convulsiones infantiles asociadas a fiebre son conocidas desde la antigüedad. En los escritos hipocráticos se señalan los hechos fundamentales de ellas: fiebre , edad de aparición y susceptibilidad individual. "Las convulsiones ocurren en niños si hay fiebre aguda, con mayor facilidad en su tercer año de vida. Los niños de mayor edad y los adultos no muestran esta propensión, a menos que precedan síntomas de mayor intensidad y peores". Las convulsiones febriles constituyen actualmente uno de los más importantes problemas pediátricos en razón de su elevada prevalencia y de la controversia existente sobre su delimitación, pronóstico y tratamiento. A pesar de la gran cantidad de datos publicados sobre el tema, resulta difícil obtener comparaciones significativas de los diversos estudios, debido a la falta de homogeneidad en los datos y en la selección de pacientes.