73 research outputs found
Comentário sobre: "Epidemiologia das internações por doença falciforme no Brasil", de Loureiro & Rozenfeld
Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide
Abstract Background Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis. Objective We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition. Results 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100–800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions. Conclusion AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing
The Value Proposition for Identity Federations
17 pagesEducation and research institutions around the world are facing significant resource challenges
that impact their ability to offer a modern collaborative environment. Campus infrastructure,
from the network (both wired and wireless) up through identity management, needs to support
inter-institutional collaboration on the part of their students, faculty. In order to understand the
layers of costs and benefits involved in local, regional, and global collaboration, campus CIOs
and IT staff must understand the value proposition for a stronger network, richer services, and a
solid identity management infrastructure. In particular, establishing an identity federation to help
support the global engagement needs to have clear value at the local level as well as the regional
or global level in order to win the necessary funding in the light of all the competing needs of the
institution.
This paper attempts to bring clarity to the questions that surround the heart of the value
proposition for identity federation. Why should identity management and federation be
prioritized? What arguments can campus CIOs use to sway the local and regional funding
agencies that already have so many demands? What needs to be done to establish an identity
federation, and have it interoperate with other identity federations around the world
EOSC Authentication and Authorization Infrastructure (AAI) : Report from the EOSC Executive Board Working Group (WG) Architecture AAI Task Force (TF)
The EOSC Architecture Working Group has assigned the AAI Task Force (AAI TF) the task to establish a common global ecosystem for identity and access control infrastructures for the European Open Science Cloud (EOSC). Since the EOSC is part of an international environment of research and education, the principles established by the EOSC AAI subtask must be globally viable. The EOSC AAI TF has produced a set of deliverables: - EOSC AAI First Principles & Requirements - EOSC AAI Baseline Architecture - EOSC AAI Federation participation guidelines (participation policy and technical framework) - EOSC AAI Best Practise
Novel fibronectin mutations and expansion of the phenotype in spondylometaphyseal dysplasia with “corner fractures”
Heterozygous pathogenic variants in the FN1 gene, encoding fibronectin (FN), have recently been shown to be associated with a skeletal disorder in some individuals affected by spondylometaphyseal dysplasia with “corner fractures” (SMD-CF). The most striking feature characterizing SMD-CF is irregularly shaped metaphyses giving the appearance of “corner fractures”. An array of secondary features, including developmental coxa vara, ovoid vertebral bodies and severe scoliosis, may also be present. FN is an important extra cellular matrix component for bone and cartilage development. Here we report five patients affected by this subtype of SMD-CF caused by five novel FN1 missense mutations: p.Cys123Tyr, p.Cys169Tyr, p.Cys213Tyr, p.Cys231Trp and p.Cys258Tyr. All individuals shared a substitution of a cysteine residue, disrupting disulfide bonds in the FN type-I assembly domains located in the N-terminal assembly region. The abnormal metaphyseal ossification and “corner fracture” appearances were the most remarkable clinical feature in these patients. In addition, generalized skeletal fragility with low-trauma bilateral femoral fractures was identified in one patient. Interestingly, the distal femoral changes in this patient healed with skeletal maturation. Our report expands the phenotypic and genetic spectrum of the FN1-related SMD-CF and emphasizes the importance of FN in bone formation and possibly also in the maintenance of bone strength.Peer reviewe
PURA-Related Developmental and Epileptic Encephalopathy Phenotypic and Genotypic Spectrum
Background and Objectives Purine-rich element-binding protein A (PURA) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotypic spectrum of PURA syndrome by collecting data, including EEG, from a large cohort of affected patients. Methods Data on unpublished and published cases were collected through the PURA Syndrome Foundation and the literature. Data on clinical, genetic, neuroimaging, and neurophysiologic features were obtained. Results A cohort of 142 patients was included. Characteristics of the PURA syndrome included neonatal hypotonia, feeding difficulties, and respiratory distress. Sixty percent of the patients developed epilepsy with myoclonic, generalized tonic-clonic, focal seizures, and/or epileptic spasms. EEG showed generalized, multifocal, or focal epileptic abnormalities. Lennox-Gastaut was the most common epilepsy syndrome. Drug refractoriness was common: 33.3% achieved seizure freedom. We found 97 pathogenic variants in PURA without any clear genotype-phenotype associations. Discussion The PURA syndrome presents with a developmental and epileptic encephalopathy with characteristics recognizable from neonatal age, which should prompt genetic screening. Sixty percent have drug-resistant epilepsy with focal or generalized seizures. We collected more than 90 pathogenic variants without observing overt genotype-phenotype associations
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