RESUMEN
Hereditary Xerocytosis (HX) is an autosomal dominantly inherited congenital hemolytic anemia associated with erythrocyte dehydration due to decreased intracellular potassium content resulting in increased mean corpuscular hemoglobin concentration. The affected members of HX families show compensated anemia with splenomegaly, hemosiderosis, and perinatal edema but are in large part transfusion independent. Functional studies show a link between mutations in mechanosensitive ion channel, encoded by PIEZO1 gene and the HX. We identified new PIEZO1 variants that are likely pathogenic in three phenotypically characterized multi-generational HX Brazilian families. Interestingly, one missense variant of the PIEZO1 gene identified, p.E2494V was associated in trans with the previously reported most frequent pathogenic duplication p.E2496ELE. The three-dimensional structure of the human protein modeled using structural coordinates of the mouse Piezo1 solved by cryo-electron microscopy (Cryo-ME) showed that the two identified variants, p.M2007L and p.T2014I, are localized to an important mechanosensitive transmembrane domain suggesting a conformational mechanism for altered channel's gating. The p.E2496ELE variant identified alters the extension of helix α1 bringing it much closer to the beam affecting the position of it structure at the end of the pore.
Asunto(s)
Anemia Hemolítica Congénita/genética , Hidropesía Fetal/genética , Canales Iónicos , Mutación Missense , Adolescente , Adulto , Sustitución de Aminoácidos , Animales , Niño , Femenino , Humanos , Recién Nacido , Canales Iónicos/química , Canales Iónicos/genética , Masculino , Ratones , Persona de Mediana Edad , Conformación Proteica en Hélice alfa , Dominios ProteicosRESUMEN
Haemoglobin (Hb) SC disease is the second most common subtype of sickle cell disease and is potentially fatal. This study aimed to determine the clinical characteristics, outcome and predictors of mortality in HbSC disease patients, and to compare these findings with patients followed-up in different centres. Clinical, laboratory and outcome data were collected from a cohort of adult patients with HbSC disease followed between 1991 and 2103. Cox regression multivariate analysis was used to determine predictors of mortality. One hundred and fifty-five patients were followed-up over 20 years: 9% died and 70·8% had at least one complication. The most common complications were: painful crises (38·3%), retinopathy (33·8%), cholelithiasis (30·3%), osteonecrosis (24·8%) and sensorineural hearing disorders (9·7%). Frequency of chronic complications was similar in most studies. In multivariate analysis, hearing disorders remained an independent predictor of mortality (Odds Ratio 9·26, 95% confidence interval 1·1-74·8; P = 0·03). It was concluded that patients with HbSC disease receive a late diagnosis and there is remarkable similarity between the studies conducted in different centres around the world. Sensorineural hearing disorders were an independent predictor of mortality, suggesting that it may be useful to implement routine diagnostic screening.
Asunto(s)
Enfermedad de la Hemoglobina SC/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Colelitiasis/etiología , Comorbilidad , Diagnóstico Tardío , Femenino , Estudios de Seguimiento , Pérdida Auditiva Sensorineural/etiología , Pérdida Auditiva Sensorineural/mortalidad , Enfermedad de la Hemoglobina SC/sangre , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/diagnóstico , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Osteonecrosis/etiología , Dolor/etiología , Embarazo , Complicaciones Hematológicas del Embarazo/epidemiología , Modelos de Riesgos Proporcionales , Enfermedades de la Retina/etiología , Adulto JovenRESUMEN
We report a rare case of aseptic arthritis in the temporomandibular joint of a patient with sickle cell anemia. A 22-year-old woman with sickle cell disease, in the 18th week of gestation, was referred by her hematologist to investigate a sudden mouth opening limitation and severe pain on her left cheek. The patient received a standard pain assessment protocol, clinical examination, and complementary exams (complete blood count, hemoglobin electrophoresis, blood solubility test, panoramic radiograph, and magnetic resonance imaging [MRI]). The blood results were consistent with a sickle cell crisis and the MRI showed an inflammatory process around the left temporomandibular joint. Treatment with opioid analgesics and blood transfusion provided good results. Sickle cell anemia is a disease that can cause arthritis of the temporomandibular joint, and although it is rare, clinicians should be attentive to the differential diagnosis in patients with this disease.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Dolor Facial/tratamiento farmacológico , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Articulación Temporomandibular/patología , Analgésicos Opioides/uso terapéutico , Anemia de Células Falciformes/terapia , Antiinflamatorios no Esteroideos/uso terapéutico , Dolor Facial/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Dimensión del Dolor , Embarazo , Radiografía Panorámica , Adulto JovenRESUMEN
As porfirias são doenças incomuns e de herança genética na maior parte doscasos. As porfirias são divididas em eritropoiéticas, hepáticas agudas e hepáticas crônicas. Os subtipos de maior relevância clínica são a porfiria cutânea tarda e a porfiria intermitenteaguda. O diagnóstico das porfirias pode ser bastante difícil, dada a sobreposição de quadros clínicos e achados bioquímicos. A precisão do diagnóstico depende da dosagem de porfirinasurinárias e fecais, da análise da atividade enzimática de eritrócitos e, eventualmente, da pesquisa de mutações. O objetivo do presente artigo é realizar revisão literária das porfirias,com ênfase no diagnóstico e tratamento de seus diversos subtipos...
Porphyrias are uncommon diseases that have genetic inheritance in the majorityof the cases. Porphyrias are divided in: erythropoietic porphyria, acute hepatic porphyria and chronic hepatic porphyria. The subtypes with major clinical relevance are porphyria cutaneatarda and acute intermittent porphyria. Diagnosing porphyrias may be quite difficult, as there is significant overlapping between clinical and biochemical findings. The diagnosis depends on the measurement of urinary and fecal porphyrins, enzymatic analysis of erythrocytes and, eventually, analysis of mutations. The main purpose of this article is to make a review of porphyrias, with emphasis on diagnosis and treatment of its several subtypes...
Asunto(s)
Humanos , Porfiria Intermitente Aguda/diagnóstico , Porfiria Cutánea Tardía/diagnóstico , Porfirias/diagnóstico , Porfirias/genéticaRESUMEN
The literature describing tuberculosis (TB) in hematopoietic stem cell transplant (HSCT) recipients is scant, even in countries where TB is common. We describe a case of pulmonary TB in a patient who underwent HSCT and review the English language literature on this subject. An extensive PubMed and Ovid search was undertaken for the period January 1980 to March 2009; the search terms used were 'Mycobacterium tuberculosis' or 'tuberculosis', in combination with 'hematopoietic stem cell transplantation' or 'bone marrow transplantation'. The patient in the present case report underwent allogeneic transplantation and developed TB 8 days after his HSCT. The patient had received vaccination against TB in childhood. During the year prior to the HSCT he had had contact with a relative who had pulmonary TB. On day 3 of anti-TB treatment he developed pericarditis. The patient received anti-TB treatment for 6 months without major problems. From the literature review, we found 34 related studies, 25 on the clinical manifestations of TB. Most of the reports were from Asia (48%), and the incidence of TB varied from 0.0014% in the USA to 16% in Pakistan. TB occurred at between +21 and +1410 days post-HSCT (257.2 days the median), and the lung was the organ most frequently involved. Mortality varied from 0% to 50% and was higher in allogeneic HSCT. There is no consensus regarding screening with the tuberculin skin test or primary prophylaxis for latent TB, and further research into this is necessary in developing countries with a high prevalence of TB.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Tuberculosis Pulmonar/etiología , Antituberculosos/uso terapéutico , Brasil , Humanos , Masculino , Pericarditis Tuberculosa/diagnóstico por imagen , Pericarditis Tuberculosa/tratamiento farmacológico , Pericarditis Tuberculosa/etiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Trasplante Homólogo , Tuberculosis Pulmonar/diagnóstico , Tuberculosis Pulmonar/diagnóstico por imagen , Tuberculosis Pulmonar/tratamiento farmacológico , Adulto JovenRESUMEN
A anemia ferropriva grave secundária à hemorragia digestiva por angiodisplasias intestinais representa um grande desafio terapêutico. Comumente, as ectasias vasculares são múltiplas e dispersas ao longo do intestino, limitando a eficácia do tratamento hemostático local. Nos últimos anos houve significativo avanço no tratamento anti-angiogênico sistêmico das angiodisplasias intestinais, sendo talidomida a droga mais empregada para tal fim. Relatamos o caso de uma paciente de 49 anos com angiodisplasias intestinais secundárias a síndrome CREST (Calcinose, Raynaud, Dismotilidade Esofágica, Esclerodactilia e Telangiectasias). A paciente apresentava quadro de melena recorrente e alta necessidade transfusional, e não obteve resposta clínica após realização de enteroscopia e eletro-coagulação das lesões com plasma de argônio. Após a introdução de talidomida 100mg ao dia, a paciente evoluiu de forma bastante satisfatória. O caso apresentado neste texto, além de demonstrar sucesso da talidomida no tratamento de angiodisplasias intestinais refratárias à eletro-coagulação com plasma de argônio, também revela eficácia da droga na situação específica da síndrome CREST. Tal fato pode ser de grande valia quando da abordagem de hemorragia intestinal por angiodisplasias nesses pacientes, representando nova opção terapêutica...
The severe ferropenic anemia secondary to digestive bleeding due to intestinal angiodisplastic lesions represents a great challenge. Commonly, angiodisplastic lesions are multiples and disperse through the intestine and that fact limits local treatments. Over the last years, there was a great advance in the antiangiogenic treatment of intestinal angiodisplastic lesions and thalidomide was the most employed drug for this purpose. We report a case of a 49 year-old patient with intestinal angiodisplastic lesions due to CREST syndrome (Calcinosis, Raynaud phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia). The patient presented repeated episodes of digestive bleeding and did not achieve clinical improvement after enteroscopy and argon plasma coagulation. The treatment consisting of the introduction of thalidomide 100mg per day demonstrated success. The case presented in this text reveals success in the use of thalidomide in the treatment of intestinal angiodisplastic lesions, probably representing a new therapeutic option...
Asunto(s)
Angiodisplasia/terapia , Electrocoagulación , Síndrome CREST/terapia , Talidomida/uso terapéuticoRESUMEN
INTRODUCTION: Head trauma is an important consequence of child abuse. Specific pathophysiological mechanisms in child abuse are responsible for the ''whiplash shaken-baby syndrome'', which would favour the occurrence of intracranial hemorrhages. CASE REPORT: We report the case of a child who developed epidural hematoma following minor-intensity head trauma. Initial diagnosis of child abuse was made, but subsequent investigation led to the diagnosis of hemophilia A. CONCLUSION: Even though epidural hematoma is not closely associated with child abuse, this aethiology must always be considered when the reported trauma mechanism is out of proportion to the magnitude of the encountered lesions
Asunto(s)
Humanos , Masculino , Lactante , Maltrato a los Niños/diagnóstico , Hematoma Epidural Craneal , Hemofilia A/diagnóstico , Traumatismos Craneocerebrales/complicaciones , Diagnóstico Diferencial , Hematoma Epidural CranealRESUMEN
INTRODUCTION: Head trauma is an important consequence of child abuse. Specific pathophysiological mechanisms in child abuse are responsible for the "whiplash shaken-baby syndrome", which would favour the occurrence of intracranial hemorrhages. CASE REPORT: We report the case of a child who developed epidural hematoma following minor-intensity head trauma. Initial diagnosis of child abuse was made, but subsequent investigation led to the diagnosis of hemophilia A. CONCLUSION: Even though epidural hematoma is not closely associated with child abuse, this etiology must always be considered when the reported trauma mechanism is out of proportion to the magnitude of the encountered lesions.