Intellectual disability, coarse face, relative macrocephaly, and cerebellar hypotrophy in two sisters

We report on two Portuguese sisters with a very similar phenotype characterized by severe intellectual disability, absent speech, relative macrocephaly, coarse face, cerebellar hypotrophy, and severe ataxia. Additional common features include increased thickness of the cranial vault, delayed dental eruption, talipes equino-varus, clinodactyly, and camptodactyly of the fifth finger. The older sister has retinal dystrophy and the younger sister has short stature. Their parents are consanguineous. We suggest this condition constitutes a previously unreported autosomal recessive entity.

Prevalencia de anticuerpos a Neospora caninum en hatos de bovinos lecheros en tres parroquias del cantón Cuenca, Ecuador

La actividad ganadera es una de las principales fuentes de trabajo en nuestro país y particularmente en nuestra provincia, actividad donde la reproducción es uno de los pilares que sostienen la productividad y eficiencia. Estas se ven disminuidas por enfermedades como la neosporosis que, al causar abortos, muerte embrionaria, nacimiento de terneros con ataxia y problemas neuromusculares, etc., produce pérdidas económicas. En el año 2005 no existían en el país datos epidemiológicos de este agente, por lo que se planteó el estudio como para diagnosticar con alta sensibilidad y especificidad, la presencia de anticuerpos a Neospora caninum en hatos lecheros de las parroquias con mayor producción lechera. Los objetivos que se plantearon en el estudio fueron: Determinar la existencia de anticuerpos contra Neospora caninum, mediante la prueba de ELISA, en hembras bovinas de las parroquias de Tarqui, Cumbe y Victoria del Portete Determinar la prevalencia a Neospora caninum en función de la procedencia, la edad, la raza de los animales y los antecedentes de abortos.

A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

International audience

Clinical Signs and Symptoms and Laboratory Findings of Methadone Poisoning in Children

Background: Poisoning accounts for about 7% of all accidents in children under 5 years and is implicated in over 5% of all childhood deaths in developing countries. Objectives: Due to the potential risks of methadone poisoning in children and increased cases of methadone poisoning among Iranian children, this study was conducted to investigate the clinical signs and symptoms and laboratory findings of methadone toxicity in children. Patients and Methods: The present retrospective, descriptive, cross-sectional study describes the clinical symptoms and signs and laboratory findings of methadone poisoning in children under 12 years old in Shahid Beheshti Hospital, Kashan, during the years 2009 to 2013. Results: Of 58 patients, 33 (56.9%) were male and 25 (43.1%) female (P = 0.294). The mean age of patients was 5.2 ± 1.0 years. All the cases of poisoning happened with methadone syrup, due to unsafe keeping of methadone in mineral water bottles and containers of other drugs. Signs and symptoms included drowsiness (91.4 %), miosis (75.9%), vomiting (69.0%), ineffective breathing (any kind of breathing problem except apnea) (62.1%), apnea (53.4%), cyanosis (43.1%), seizure (8.6%), ataxia (6.9%) and delirium (3.4%). Conclusions: Keeping methadone in appropriate containers and warning methadone consumers about the dangerous side effects of its consumption and the symptoms of methadone poisoning in children may minimize the occurrence of this form of poisoning and its complications in children.

Different Kinds of Paraneoplastic Syndromes in Childhood Neuroblastoma

Background: Clinical presentations of paraneoplastic syndromes in neuroblastoma may multiply. Review of the clinical data and the literature on this syndrome may help in the diagnosis of neuroblastoma. Objectives: In order to make more accurate diagnosis, we reviewed the clinical data and the literature on this syndrome. Patients and Methods: Between April 2007 and April 2012, 68 children were diagnosed with neuroblastoma or ganglioneuroblastoma in our institution, 9 of which presented exclusively with paraneoplastic syndromes and were not treated with chemotherapy prior to diagnosis. After the diagnosis, all patients received chemotherapy and operation on NB97 protocol. Results: Among 68 pediatric patients with neuroblastoma or ganglioneuroblastoma, 4 (5.9%) patients suffered from neurological complications at diagnosis, 2 (2.9%) patients had digestive tract disorders, 2 (2.9%) patients had immune diseases, and 1 (1.5%) suffered from hematological disorder (without bone marrow involvement). All paraneoplastic syndrome patients achieved complete remission on paraneoplastic syndrome before completion of chemotherapy. Conclusions: Neuroblastoma may present with a range of non-specific neurologic symptoms in addition to the well-known opsoclonus-myoclonus syndrome and cerebellar ataxia. In any case, the presence of unexplained neurologic manifestations and other common clinical presentations such as rash, constipation, diarrhea, and especially immune disorders in an otherwise healthy child had raised the possibility of paraneoplastic syndrome due to the presence of an undiagnosed tumor.

Multifactorial approach to non-viral gene therapy: development of an efficient system for the retina

Tese de Doutoramento, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2016

The Herpesvirus Nuclear Egress Complex Component, UL31, is Recruited to Sites of DNA Damage Through Poly(ADP-RIBOSE) Binding

Thesis (Master, Biomedical & Molecular Sciences) -- Queen's University, 2016-08-23 15:03:30.807

Neurodegeneration and the m-AAA protease: pathogenic cascades in neurons and myelinating cells

The m-AAA protease is a hexameric complex involved in processing of specific substrates and turnover of misfolded polypeptides in the mitochondrial inner membrane. In humans, the m-AAA protease is composed of AFG3L2 and paraplegin. Mutations in AFG3L2 have been implicated in dominant spinocerebellar ataxia (SCA28) and recessive spastic ataxia-neuropathy syndrome (SPAX5). Mutations of SPG7, encoding paraplegin, are linked to hereditary spastic paraplegia. In the mouse, a third subunit AFG3L1 is expressed. Various mouse models recapitulate the phenotype of these neurodegenerative disorders, however, the pathogenic mechanism of neurodegeneration is not completely understood. Here, we studied several mouse models and focused on cell-autonomous role of the m-AAA protease in neurons and myelinating cells. We show that lack of Afg3l2 triggers mitochondrial fragmentation and swelling, tau hyperphosphorylation and pathology in Afg3l2 full-body and forebrain neuron-specific knockout mice. Moreover, deletion of Afg3l2 in adult myelinating cells causes early-onset mitochondrial abnormalities as in the neurons, but the survival of these cells is not affected, which is a contrast to early neuronal death. Despite the fact that myelinating cells have been previously shown to survive respiratory deficiency by glycolysis, total ablation of the m-AAA protease by deleting Afg3l2 in an Afg3l1 null background (DKO), leads to myelinating cell demise and subsequently progressive axonal demyelination. Interestingly, DKO mice show premature hair greying due to loss of melanoblasts. Together, our data demonstrate cell-autonomous survival thresholds to m-AAA protease deficiency, and an essential role of the m-AAA protease to prevent cell death independent from mitochondrial dynamics and the oxidative capacity of the cell. Thus, our findings provide novel insights to the pathogenesis of diseases linked to m-AAA protease deficiency, and also establish valuable mitochondrial dysfunctional mouse models to study other neurodegenerative diseases, such as tauopathies and demyelinating diseases.

Estado de las enfermedades raras que cursan con discapacidad intelectual en Colombia

Las enfermedades raras o huérfano son una problemática que ha tomado mucha importancia en el contexto mundial del presente siglo, estas se han definido como crónicas, de difícil tratamiento de sus síntomas y con baja prevalencia en la población; muchas de estas enfermedades cursan con varios tipos de discapacidad, siendo el objetivo del presente trabajo el enfocarse en aquellas enfermedades raras que cursan con discapacidad intelectual. Para poder profundizar en estas enfermedades se realizó una revisión teórica sobre las enfermedades raras, así como de la discapacidad psíquica y su importancia a nivel mundial y nacional. A partir de estas definiciones, se revisaron en profundidad 3 enfermedades raras que cursan con discapacidad intelectual en el contexto colombiano, como son: el síndrome de Rett, el síndrome de Prader-Willi y el síndrome de X frágil. En cada una de estas enfermedades además se explicaron los tipos de diagnóstico, intervención, prevención, grupos de apoyo y tipos de evaluación que más se usan en el contexto nacional