A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree.

Generalized epilepsy with febrile seizures plus (GEFS+) is an inherited epileptic syndrome with a marked clinical and genetic heterogeneity. Here we report the molecular characterization of a large pedigree with a severe clinical form of GEFS+. Genetic linkage analysis implied the involvement of the FEB3 in the disease phenotype of this family (parametric two-point lod-score of 2.2). Sequencing of the SCN1A gene revealed a novel aspartic acid for glycine substitution at position 1742 of this sodium channel subunit. The amino-acid replacement lies in the pore-forming region of domain IV of SCN1A. Our observations are consistent with the genotype-phenotype correlation studies suggesting that mutations in the pore-forming loop of SCN1A can lead to a clinically more severe epileptic syndrome.

A CLN5 mutation causing an atypical neuronal ceroid lipofuscinosis of juvenile onset.

Three related patients from Colombia presented with a juvenile-onset neuronal ceroid lipofuscinosis. Electron microscopy of one case showed condensed fingerprint profiles, and genetic analyses identified a novel missense mutation in CLN5. The authors demonstrate the existence of pathogenic CLN5 mutations outside northern Europe and that mutations in this gene can lead to an atypical late-onset neuronal ceroid lipofuscinosis disease, in addition to the late infantile form first described in Finland.

[Clinical characterisation and power simulations to detect genetic linkage in attention deficit hyperactivity disorder in Antioquian families]. / Caracterización clínica y simulaciones de poder para ligamiento genético en el trastorno por déficit de atención con hiperactividad en familias antioqueñas.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurobehavioural disorder whose essential characteristic is a persistent pattern of inattention or hyperactivity and impulsiveness. Recent studies into prevalence carried out on the Antioquian population by our group found an overall prevalence of 15.8%, which confirms ADHD as one of the most frequent problems in infancy. The cause of this disorder is still not altogether clear; familial aggregation of ADHD points towards a genetic component. Although to date no model of inheritance has been defined, its high prevalence rate, the difficulties involved in its diagnosis and its effects on the cognitive functions, as well as the social and educational repercussions, make this disorder a problem in children's public health. AIMS: Our aim was to carry out power simulations to detect genetic linkage. PATIENTS AND METHODS: The Slink programme, which is part of Linkage package, was used in six families from the city of Medellín Antioquia, which is a region where a founding effect is likely to have taken place; this makes it a strategic zone for genetic linkage studies in complex diseases such as ADHD. RESULTS: Assuming the population to be homogenous, the lod score (Z) is greater than 3 (Z>3) and individual lod score values of between 0 and 6 were obtained for each family. CONCLUSIONS: In this paper we discuss the benefits of having multigenerational families, in Antioquia, to conduct gene mapping studies and we examine the different strategies to be developed with the findings reported here.

[Cerebrovascular disease in children with sickle cell anaemia]. / Enfermedad cerebrovascular en niños con anemia de células falciformes.

INTRODUCTION: Cerebrovascular disease (CVD) is one of the most clinically devastating complications in children with sickle cell anaemia (SCA) and an important cause of death in this population. AIMS: To determine the incidence of CVD in children with SCA and to characterise the risk factors and other related clinical and imaging aspects. PATIENTS AND METHODS: We conducted a retrospective, cross sectional, descriptive study of paediatric patients with SCA and CVD that covered the period between January 1992 and February 2002. RESULTS: A total of 131 children with SCA were registered in the period between January 1992 and February 2002, during which five children suffered some kind of CVD event. This figure corresponds to 3.81% of the patients with SCA and 7.69% of the total number of children with CVD. The most frequent clinical presentation of the CVD is bouts of seizures and the most frequently observed type of CVD is ischemic, chiefly located in the middle cerebral artery. Of the different predictors that exist for ischemic CVD, haemoglobin count was found to be lower than in haemorrhagic CVD. CONCLUSION: CVD is a common complication in the progress of patients with SCA with a high percentage of neurological sequelae.

[Clinical and radiological findings in two cases of aspergillosis of the central nervous system in children]. / Hallazgos clínicos y radiológicos de dos casos de aspergilosis del sistema nervioso central en niños.

INTRODUCTION: Aspergillosis is the second fungemia after candidiasis that affects the central nervous system of immunodeppresed and immunocompetent humans. The literature reports nearly always compromised adults. CASE REPORTS: Two pediatric cases of central nervous system aspergillosis with different clinical course are presented. The first of them, is a immunocompetent person in whom a granulomatous disease of the central nervous system was suspected. The cultivation of stereotaxic biopsy reported thin septated hyphae. After 42 days of treatment with itraconazol the patient recovered completely. The second patient, had an acute lymphoblastic leukemia and developed a widespread aspergillosis including the central nervous system. In spite of antifungic treatment for 63 days, he died of heart failure. CONCLUSIONS: Diagnosis of aspergillosis is difficult because of the poor specificity of the neuroimages, cerebrospinal fluid and complementary labs. The images are indistinguishable from acute ischemia infarcts and later those images change to abscesses. Direct KOH staining and the cultivation of biopsed samples confirmed the diagnosis of aspergillosis. An aggressive treatment with amphotericin B and itraconazol is recommended, but high mortality is suspected. Diagnosis, neuroimaging, clinical evolution and treatment are discussed.

[Clinical characteristics of optical neuritis in children]. / Características clínicas de la neuritis óptica en niños.

OBJECTIVE: To describe the clinical characteristics and the visual prognosis of a group of children affected with optic neuritis. PATIENTS AND METHODS: The clinical charts of patients under 15 years of age with clinical criteria of optic neuritis were revised at the Hospital Universitario San Vicente de Pa l (Medell n, Colombia), in a time span from January 1th 1989 to December 31th 2001. RESULTS: 16 patients fulfilled the clinical criteria of optic neuritis; 50% were male and the overall mean age was 9,4 years. Seven (43,7%) patients had a preceding infectious disease two weeks earlier and only one suffered from varicella four weeks earlier. Decrease in visual acuity was present in 15 (94%) patients; 7 (44%) had headache; 7 (44%) had ocular ache and 25% had both, head and ocular ache. Neuritis was found in 28 eyes, of whom 68% had papilledema and in 32% the fundoscopic examination was normal. Bilateral affection was present in 75%. Excellent visual prognosis (20/20) was present in 19 (68%) of affected eyes; good (20/20 to 20/50) in 4 (14%), regular (20/50 to 20/100) in 2 (7%) and bad (20/200) in 11%. CONCLUSION: In our country the clinical evolution of childhood optic neuritis does not differ from that reported in other parts of the world.

[Subacute combined degeneration. A description of the case of a strictly vegetarian child]. / Degeneración combinada subaguda. Descripción de un caso en un niño vegetariano estricto.

INTRODUCTION: Cyanocobalamin (vitamin B12) is an essential cofactor of various metabolic pathways. Lack of it leads to symptoms which may be constitutional, of skin or mucous membranes, hematological or neuropsychiatric disorders. Neurological involvement in adults has been well described and analyzed in the literature, however there are fewer cases of children. In the cases described in children the deficiency was related to maternal malnutrition, and socioeconomic and cultural problems. Since vegetarianism is a custom followed by different social groups we wish to draw attention to this as a cause of vitamin B12 deficiency and the neurological disorder this may cause. CLINICAL CASE: We describe the case of a 10 year old boy, a member of a religious community who were strict vegetarians. Over three months he developed: a cognitive disorder, pyramidal syndrome of his legs, involvement of the posterior spinal cord, peripheral motor and sensory alterations which, together with the complementary investigations, was found to be compatible with subacute combined degeneration due to vitamin B12 deficiency. CONCLUSION: We draw attention to the clinical and laboratory aspects of this disorder and the importance of taking the possibility of this diagnosis into account in children with nutritional risk factors.

Malformacion aneurismatica de la vena galeno / Vein of galen aneurysmatic malformation

Se estudiaron tres niñas y dos niños con malformación aneurismática de la vena de Galeno ( MAVG), tanto clínica como radiológicamente, durante 4 años. Dos tipos de angioarquitectura se encontraron y explican porque las macro fístulas del tipo coroidal que tenían tres pacientes se tuvieron que tratar con embolización agresiva por terapia endovascular, dado el gran compromiso neurológico. El cuarto caso se trataba de una MAVG de tipo mural en una niña asintomática que solamente presentaba macrocránea y en la que la familia no permitía ninguna intervención terapéutica. El quinto caso fue un hallazgo incidental en cirugía, ya que la resonancia y la angiografía fueron negativas para malformación vascular

Paragonimosis in the Cajabamba and Condebamba districts, Cajamarca, Peru.

Stool samples from 409 pre-school and school students, living in six villages of the Cajabamba and Condebamba districts, Cajamarca, Perú, were examined using wet preparations and Lumbreras' method, looking for Paragonimus eggs. Fecal and sputum samples from two children (0. 5%) of 6 and 8 year-old showed eggs of Paragonimus. One hundred and twenty freshwater crabs, Hypolobocera chilensis eigenmanni, were collected from the Condebamba valley and 21 (17.5%) of them were infected with P. mexicanus (syn. P. peruvianus) metacercariae. Our results show the persistence of Paragonimus in human beings and in the main source of infection, the crabs.

Identification of functional domains of Bordetella dermonecrotizing toxin.

Bordetella dermonecrotizing toxin (DNT) stimulates the assembly of actin stress fibers and focal adhesions by deamidating Gln63 of the small GTPase Rho. To clarify the functional and structural organization of DNT, we cloned and sequenced the DNT gene and examined the functions of various DNT mutants. Our analyses of the nucleotide and amino acid sequences revealed that the start codon of the DNT gene is a GTG triplet located 39 bp upstream of the reported putative initiation ATG codon; consequently, DNT contains an additional 13 amino acids at its N-terminal end. All of the N-terminally truncated mutants were found to modify Rho. The shortest fragment of DNT possessing the Rho modification activity consists of amino acids from Ile1176 to the C-terminal end. This fragment overlaps the region homologous to Escherichia coli cytotoxic necrotizing factors (CNFs), which show activity similar to that of DNT. The introduction of a mutation at Cys1305 located in the highly conserved region between CNFs and DNT eliminated the activity, indicating that this domain is the catalytic center of DNT. The N-terminal fragment (1 to 531) of DNT failed to modify Rho but reduced the DNT-induced polynucleation in MC3T3-E1 cells when simultaneously added with the holotoxin, suggesting competitive inhibition in the receptor-binding or internalizing step. Our finding that DNT consists of an N-terminal receptor-binding and/or internalizing domain and a C-terminal catalytically active domain may facilitate analysis of the overall action of the toxin on the mammalian target cells.

Prevalencia de Bordetella en niños de la ciudad de Lima / Prevalence of Bordetella in children in Lima

Se estudiaron 287 hisopados nasofaríngeos, procedentes de niños entre 1 mes y 12 años de edad, atendidos en el Hospital del Niño, ciudad de Lima. Dichos pacientes, tenían en su mayor parte diagnóstico de tos ferina. Las muestras tomadas se sembraron en el medio de Bordet-Gengou, identificándose las colonias por características culturales, pruebas bioquímicas y/o aglutinaciones. Se aislaron en 5 casos cepas de Bordetella, lo que representa el 17.86% de las muestras estudiadas. Dos de las cepas pudieron ser identificadas como B. parapertussis y B. pertussis, respectivamente. Se pone de manifiesto la importancia del aislamiento de B. parapertussis de un paciente con síntomas típicos de tos ferina.

28 pharyngeal swabs were studied in children who attended to the Children Hospital from Lima. Most of children had clinical diagnosis of whooping cough. The samples were seeded on Bordet Gengou Medium and identified by morphology culture, physiological characteristics, and agglutination test. Five strains of Bordetella were isolated. Two strains were identified as B. parapertussis and B. pertussis, respectively. It was indicated the importance of B. parapertussis isolation from a patient with typical whooping cough symptoms.