RESUMO
Fabry disease is an invalidating multisystemic disorder affecting α-Galactosidase, a rate-limiting hydrolase dedicated to lipid catabolism. Non-metabolized substrates, such as Globotriaosylceramide and its derivatives trigger the direct or indirect activation of inflammatory events and endothelial dysfunction. In spite of the efficacy demonstrated by enzyme replacement therapy or pharmacological chaperones in delaying disease progression, few studies have analyzed whether these treatments can improve the pro-inflammatory state of FD patients. Therefore, the aim of this work was to assess cytokines and cardiovascular risk-related proteins detectable in plasma from FD patients, whether treated or not with ERT, to evaluate the reliability of these markers in monitoring disease stage and treatment effects. We identified inflammatory and endothelial dysfunction markers (ADAMTS-13, TNF-α, GDF-15, MIP-1ß, VEGFA, MPO, and MIC-1) that cooperate in a common pathway and are increased in FD patients' plasma samples. As shown by the assessment of these proteins over time, they can help to evaluate the risk of higher severity in FD, as well as ERT effects. Even though the analyzed proteins cannot be considered as proper biomarkers due to their non-specificity to FD, taken together they can provide a signature of reference molecules with prognostic value for early diagnosis, and evaluation of disease progression and treatment efficacy, using blood samples.
Assuntos
Biomarcadores , Progressão da Doença , Doença de Fabry , Humanos , Doença de Fabry/sangue , Doença de Fabry/diagnóstico , Biomarcadores/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Inflamação/sangue , Citocinas/sangue , Citocinas/metabolismo , Terapia de Reposição de Enzimas , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/sangueRESUMO
Introducción. La variante conductual de la demencia frontotemporal se caracteriza por el deterioro progresivo de la personalidad, social y cognitivo que se asocia con diversas patologías moleculares de la degeneración lobar frontotemporal (DLFT): DLFT-tau, DLFT-TDP y DLFT-FUS. El estudio anatomopatológico es necesario para su diagnóstico. Caso clínico. Varón de 61 años, con un cuadro progresivo de tres años de evolución de trastorno conductual, apatía, lenguaje pobre, perseveración, falta de empatía, bulimia y disfunción ejecutiva. En la neuroimagen se objetivó una atrofia cortical frontal de predominio derecho, y en la tomografía simple por emisión de fotón único cerebral, una hipoperfusión frontoparietotemporal bilateral con afectación de tálamos y caudados. Clínicamente, se le diagnosticó probable demencia frontotemporal, variante conductual. Tras su fallecimiento, se donó el cerebro al Banco de Tejidos Neurológicos y el diagnóstico neuropatológico fue el de degeneración corticobasal. Conclusiones. La degeneración corticobasal es una de las taupatías de la DLFT-tau. Los criterios diagnósticos de degeneración corticobasal de 2013 contemplan como fenotipo clínico la disfunción ejecutiva, las alteraciones conductuales y de personalidad similar al de este paciente. El caso anatomoclínico presentado ilustra la falta de correlación entre el fenotipo clínico y el diagnóstico neuropatológico subyacente en la demencia frontotemporal, y la necesidad de realizar el estudio histopatológico para llegar al diagnóstico definitivo
Introduction. The behavioural variant of frontotemporal dementia is characterised by progressive social, cognitive and personality deterioration associated with several molecular pathologies of frontotemporal lobar dementia (FTLD): FTLD-tau, FTLD-TDP and FTLD-FUS. Its diagnosis requires pathological studies. Case report. A 61-year-old male, with a three-year progressive history of behavioural disorder, apathy, poor language skills, perseveration, lack of empathy, bulimia and executive dysfunction. Neuroimaging revealed right-dominant frontal cortical atrophy, and a single-photon emission tomography brain scan showed bilateral frontal hypoperfusion with thalamic and caudate involvement. Clinically, he was diagnosed with probable frontotemporal dementia, behavioural variant. On his death, his brain was donated to the Neurological Tissue Bank and the neuropathological diagnosis was corticobasal degeneration. Conclusions. Corticobasal degeneration is one of the FTLD-tau tauopathies. The 2013 diagnostic criteria for corticobasal degeneration include executive dysfunction and behavioural and personality disorders similar to those of this patient as a clinical phenotype. The anatomoclinical case presented illustrates the absence of any correlation between the clinical phenotype and the underlying neuropathological diagnosis in frontotemporal dementia, and the need to conduct a histopathological study in order to reach a definitive diagnosis
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Demência Frontotemporal/etiologia , Doenças Neurodegenerativas/complicações , Disfunção Cognitiva/complicações , Gânglios da Base/patologia , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/psicologia , Tauopatias/diagnóstico por imagem , Neuroimagem , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
El estudio del incremento de la creatinina fosfoquinasa (CPK) constituye un motivo de consulta frecuente en diversas especialidades médicas. Entre las enfermedades que cursan con CPK alta se encuentran las miopatías metabólicas siendo la enfermedad de McArdle la glucogenosis muscular más frecuente. Presentamos 2 casos clínicos de pacientes derivados a nuestro servicio de reumatología para estudio de CPK elevada cuyo diagnóstico final fue enfermedad de McArdle: un hombre de 72 años, asintomático desde el punto de vista muscular, en el que se objetivó de manera casual elevación importante de CPK en una analítica de rutina y una mujer de 30 años con síntomas musculares muy leves. El electromiograma (EMG) fue normal en ambos pacientes. En ninguno de los 2 casos existía actividad de la miofosforilasa en la biopsia muscular, siendo diagnosticados de enfermedad de McArdle (AU)
A high serum level of creatine kinase (CK) is a common reason for referring to medical specialities. Myopathies are one of the causes of elevated levels of CK. McArdle disease is the most common disorder of skeletal muscle carbohydrate metabolism. The cases are presented on 2 patients who were referred to our medical consultation to study the cause of their increased CK levels: a 72 year old asymptomatic man with high levels of CK detected by chance in a routine analysis, and a 30 year old woman with very few symptoms, apart from slight muscle pain and tiredness. Electromyography was normal in both patients. There was null activity of myophosphorylase in muscle biopsy of both cases, so a diagnosis of McArdle disease was made (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Idoso , Doença de Depósito de Glicogênio Tipo V/complicações , Doença de Depósito de Glicogênio Tipo V/diagnóstico , Doença de Depósito de Glicogênio Tipo V/terapia , Glicogênio Fosforilase Muscular/uso terapêutico , Doença de Depósito de Glicogênio/complicações , Doença de Depósito de Glicogênio Tipo V/dietoterapia , Doença de Depósito de Glicogênio Tipo V/fisiopatologia , Doença de Depósito de Glicogênio Tipo V , Eletromiografia/métodos , AutoimunidadeRESUMO
La sarcoidosis es una enfermedad granulomatosa, multisistémicade etiología desconocida. Su diagnóstico es deexclusión, una vez descartadas infecciones y otras causas.Puede afectar a cualquier órgano, pero más frecuentemente apulmones y ganglios linfáticos. La piel está afectada en un25% de los casos. Su presentación como nódulos subcutáneoses rara y han sido descritos muy pocos casos de sarcoidosissubcutánea como manifestación inicial de la enfermedad.Presentamos el caso de una mujer de 27 años con unnódulo supraciliar palpable, firme e indoloro, de meses deevolución, revestido de piel normal, como único dato clínicode interés. Recidivó varias veces. La extirpación de lalesión y su posterior estudio histológico mostró granulomasno necrotizantes situados en dermis profunda e hipodermis.Las tinciones realizas para demostrar hongos, bacilos ácidoalcoholresistentes o materiales extraños resultaron negativas.Todas las exploraciones complementarias a las que fuesometida la paciente resultaron normales.Se administró tratamiento corticoesteroideo, al que respondiófavorablemente.Destacamos que la sarcoidosis debe ser considerada enel diagnóstico diferencial de enfermedades que debutan connódulos subcutáneos y así evitar exploraciones más agresivaspara su diagnóstico
Sarcoidosis is a multisystemic disease of unknown etiology.Diagnosis is made after exclusion of other granulomatousand infectious diseases.Any organ can be involved, most commonly lungs andskin. On average, 25% of sarcoidosis cases have cutaneousinvolvement. Subcutaneous nodules at the onset of the diseaseare extremely infrequent.We report the case of a 27 year-old woman who presentedwith a firm, painless subcutaneous nodule on the forehead,without involvement of the overlying skin. The lesionwas removed and relapsed several times later.Histologic examination revealed noncaseating granulomasin subcutaneous tissue and deep dermis. Special stainsfor fungi, acid-fast bacilli or foreign body material, were allnegative.Despite thorough investigations, all tests were negativeand the patient didnt have any evidence of extra-cutaneoussarcoidosis. She started on oral corticosteroids, inducing agood response.We highlight the importance of an exhaustive study ofevery single subcutaneous nodule in order to avoid a delayin the diagnosis of sarcoidosis and the unnecessary use ofmore aggressive methods