Centro Hospitalar do Porto
Repositório Científico da Unidade Local de Saúde de Santo AntónioNot a member yet
2440 research outputs found
Sort by
Genotype-Phenotype Correlations in PMM2-CDG
Get PDFPMM2-CDG is a rare disease, causing hypoglycosylation of multiple proteins, hence preventing full functionality. So far, no direct genotype-phenotype correlations have been identified. We carried out a retrospective cohort study on 26 PMM2-CDG patients. We collected the identified genotype, as well as continuous variables indicating the disease severity (based on Nijmegen Pediatric CDG Rating Score or NPCRS) and dichotomous variables reflecting the patients' phenotype. The phenotypic effects of patients' genotype were studied using non-parametric and Chi-Square tests. Seventeen different pathogenic variants have been studied. Variants with zero enzyme activity had no significant impact on the Nijmegen score. Pathogenic variants involving the stabilization/folding domain have a significantly lower total NPCRS (p = 0.017): presence of the p.Cys241Ser mutation had a significantly lower subscore 1,3 and NPCRS (p = 0.04) and thus result in a less severe phenotype. On the other hand, variants involving the dimerization domain, p.Pro113Leu and p.Phe119Leu, resulted in a significantly higher NPCRS score (p = 0.002), which indicates a worse clinical course. These concepts give a better insight in the phenotypic prognosis of PMM2-CDG, according to their molecular base.E.M. was funded by the grant titled Frontiers in Congenital Disorders of Glycosylation(1U54NS115198-01) from the National Institute of Neurological Diseases and Stroke (NINDS)and the National Center for Advancing Translational Sciences (NCATS), at the National Institute of Health. P.W. was funded by the Fonds Wetenschappelijk Onderzoek-Vlaanderen (Fundamenteel Klinisch Mandaat 18B4322N)info:eu-repo/semantics/publishedVersio
Case Report: Diffuse Polymicrogyria Associated With a Novel ADGRG1 Variant
Get PDFPathogenic variants of the ADGRG1 gene are associated with bilateral frontoparietal polymicrogyria, defined radiologically by polymicrogyria with an anterior-posterior gradient, pontine and cerebellar hypoplasia and patchy white matter abnormalities. We report a novel homozygous ADGRG1 variant with atypical features. The patient presented at 8 months of age with motor delay, esotropia, hypotonia with hyporeflexia and subsequently developed refractory epilepsy. At the last assessment, aged 12 years, head control, sitting and language were not acquired. Magnetic resonance imaging revealed diffuse polymicrogyria with relative sparing of the anterior temporal lobes, without an anterior-posterior gradient, diffuse hypomyelination and pontine and cerebellar hypoplasia. A panel targeting brain morphogenesis defects yielded an unreported homozygous ADGRG1 nonsense variant (dbSNP rs746634404), present in the heterozygous state in both parents. We report a novel ADGRG1 variant associated with diffuse polymicrogyria without an identifiable anterior-posterior gradient, diffuse hypomyelination and a severe motor and cognitive phenotype. Our case highlights the phenotypic diversity of ADGRG1 pathogenic variants and the clinico-anatomical overlap between recognized polymicrogyria syndromes.This work was supported by Foundation of Health Research Institute of Santiago de Compostela, Spain.info:eu-repo/semantics/publishedVersio
Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?
Get PDFPMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production. Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multi-center Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 μg/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned. Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG.Glycomine, Inc. was the sponsor of this study, and was involved in the study design and in the and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN) - Project ID No 739543.info:eu-repo/semantics/publishedVersio
Isolated Dysphagia: It could be the tip of the iceberg of a bigger problem
Get PDFinfo:eu-repo/semantics/publishedVersio
Secukinumab on Refractory Lupus Nephritis
Get PDFLupus nephritis (LN) is the most frequent severe organ manifestation of systemic lupus erythematosus (SLE). About 30% of patients are refractory to treatment. The authors report a case of treatment of LN with interleukin-17-targeted therapy, demonstrating its possible benefit, after reports of T helper 17 cell involvement in SLE pathogenesis. We present the case of a childbearing age woman with SLE, who developed refractory LN despite all the indicated therapeutic options. During follow up, infection with human papillomavirus was detected, a possible trigger, and the following management was based on this discovery. We currently know that cytokines play a major role in tissue damage and interleukin-17 (IL-17) seems to be a fundamental key in SLE and LN, having shown its expression in renal glomeruli and urinary sediment. Thus, it was decided to start treatment with an anti-IL-17A antibody, secukinumab. After starting secukinumab, clinical and biological features improved and complete renal response was achieved.info:eu-repo/semantics/publishedVersio
Guideline for the Prevention and Treatment of Infections Associated with Immunosuppressive Therapy for Autoimmune Diseases
Get PDFWe propose a guideline about the risk, prevention and treatment of infection in the patient under immunomodulatory or immunosuppressive therapy in the context of autoimmune or autoinflammatory disease. It is divided into three sections: drugs and associated risk of infection; immunizations; risk, prevention, and treatment of specific infections. The treatment of autoimmune diseases involves the use of immunosuppressive or immunomodulatory therapies, with an increasing number of new drugs being used. It is associated with an increased risk of infection, which may be present globally or only for specific agents, varying widely depending on the pharmacological class and even within the same class. The prevention strategy and clinical management need to be individually tailored and there are several key factors: characterization of the disease that prompts the immunosuppression, understanding of the mechanism of action of the immunosuppressive drug, knowledge of previous infections, recognition of risk factors, laboratory test results, vaccine administration, monitoring of clinical signs and symptoms and patient education.O presente protocolo aborda o risco, prevenção e tratamento da infeção no doente sob terapêutica imunomoduladora ou imunossupressoraem contexto de doença autoimune ou autoinflamatória. Subdivide-se nas seguintes secções: fármacos e risco associado de infeção; imunizações; risco, prevenção e tratamento de infeções específicas. Com um número crescente de novos fármacos em utilização nos últimos anos, o tratamento de doenças autoimunes envolve a utilização de terapêuticas imunossupressoras ou imunomoduladoras e associa-se a aumento do risco de infeção, que pode estar presente de uma forma global ou apenas para infeções por agentes específicos, variando amplamente consoante a classe farmacológica e mesmo dentro desta. Na estruturação da estratégia preventiva são fundamentais a caracterização da patologia que motiva a imunossupressão, a compreensão do mecanismo de ação do imunossupressor, a aferição de infeções prévias, o reconhecimento de fatores de risco, a realização de rastreios laboratoriais, a administração de vacinas, a educação do doente e a monitorização de sintomas e sinais clínicos, na dependência de uma gestão clínica necessariamente individualizada.info:eu-repo/semantics/publishedVersio
Gait speed in clinical and daily living assessments in Parkinson’s disease patients: performance versus capacity
No full textGait speed often referred as the sixth vital sign is the most powerful biomarker of mobility. While a clinical setting allows the estimation of gait speed under controlled conditions that present functional capacity, gait speed in real-life conditions provides the actual performance of the patient. The goal of this study was to investigate objectively under what conditions during daily activities, patients perform as well as or better than in the clinic. To this end, we recruited 27 Parkinson's disease (PD) patients and measured their gait speed by inertial measurement units through several walking tests in the clinic as well as their daily activities at home. By fitting a bimodal Gaussian model to their gait speed distribution, we found that on average, patients had similar modes in the clinic and during daily activities. Furthermore, we observed that the number of medication doses taken throughout the day had a moderate correlation with the difference between clinic and home. Performing a cycle-by-cycle analysis on gait speed during the home assessment, overall only about 3% of the strides had equal or greater gait speeds than the patients' capacity in the clinic. These strides were during long walking bouts (>1 min) and happened before noon, around 26 min after medication intake, reaching their maximum occurrence probability 3 h after Levodopa intake. These results open the possibility of better control of medication intake in PD by considering both functional capacity and continuous monitoring of gait speed during real-life conditions.info:eu-repo/semantics/publishedVersio
Decisões partilhadas em cuidados intensivos neonatais – abordagem bioética
Get PDFTechnological and therapeutic advances in neonatal intensive care have led to a decrease in neonatal morbidity and mortality in recent decades. Along with technical and scientific expertise, it is important to provide a holistic and comprehensive approach to the care of the newborn and family. The purpose of this review is to describe and analyze strategies to improve decision-making within a shared process between health professionals and caregivers at neonatal intensive care setting.
The decision-making process is not linear or immutable over time and there is no consensus on the definition of ‘shared decision’. More unanimous is the role of communication as a atherapeutic relationship pillar. Professional ethics, bioethics, and narrative medicine should be used as tools to address the vulnerabilities of families and professionals and as a way to consolidate and structure the human relational dimension intrinsic to medical practice.info:eu-repo/semantics/publishedVersio
Candidíase congénita – um desafio diagnóstico
Get PDFIntroduction: Congenital candidiasis is a rare intrauterine infection characterized by vesicular and pustular skin lesions appearing in the first six days of life.
Clinical case: The authors describe the case of a full-term infant presenting erythematous macules, vesicles and pustules involving the trunk and extremities and cervical burn-like dermatitis at birth. Mycological skin lesion culture was positive for Candida albicans. Blood culture was positive for methicillin-sensitive Staphylococcus aureus. After systemic antifungal and antibiotic therapy was started, the newborn remained asymptomatic with lesion improvement.
Discussion/ Conclusion: Herein is reported a case of congenital candidiasis in a full-term infant, with a successful recovery. The rarity of congenital candidiasis can lead to delayed diagnosis and unnecessary treatment. This case shows that fungal infection should be considered in the differential diagnosis of vesiculopustular skin lesions in neonates. Systemic therapy should be initiated if invasive candidiasis is suspected.info:eu-repo/semantics/publishedVersio
Regressão da linguagem como manifestação de epilepsia
Get PDFIntroduction: Childhood epileptic encephalopathies are age-dependent brain disorders in which ictal and interictal epileptogenic activity is the apparent cause of progressive cognitive and neuro-psychological impairment.
Case report: A previously healthy four-year-old boy presented to the Emergency Department with a history of receptive and expressive language regression with four days of evolution, associated with seizure onset. Clinical features and electroencephalographic findings led to diagnosis of Landau-Kleffner syndrome. The boy was treated with valproate, clobazam, and prednisolone, with language improvement.
Discussion/Conclusion: Landau-Kleffner syndrome is a rare epileptic encephalopathy with pathognomonic sudden aphasia, epilepsy, and paroxysmal electroencephalographic abnormalities. The condition should be suspected in children with normal development who show a deterioration of established language skills. Early diagnosis and treatment are important to improve outcome.info:eu-repo/semantics/publishedVersio