RESUMO
Fabry disease is an X-linked metabolic storage disorder due to the deficiency of lysosomal alpha-galactosidase A which causes accumulation of glycosphingolipids, primarily globotriaosylceramide, throughout the body. Gastrointestinal signs and symptoms-abdominal pain, nausea, diarrhea and diverticular disease--are some of the most frequently reported complaints in patients with Fabry disease but are often neglected. Gastrointestinal symptoms are due to intestinal dysmotility as well as impaired autonomic function, vasculopathy and myopathy. Since 2001, enzyme replacement therapy has been a mainstay in treatment of gastrointestinal symptoms of Fabry disease (FD), resulting in reduced gastrointestinal symptoms. Here, we report on four patients with Fabry disease (FD) who manifested early gastrointestinal involvement.
Assuntos
Doença de Fabry/diagnóstico , Doença de Fabry/metabolismo , Gastroenteropatias/diagnóstico , Gastroenteropatias/metabolismo , Trato Gastrointestinal/metabolismo , Adolescente , Adulto , Animais , Biomarcadores , Encéfalo/metabolismo , Encéfalo/patologia , Criança , Comorbidade , Diagnóstico Diferencial , Doença de Fabry/etiologia , Feminino , Gastroenteropatias/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
BACKGROUND: Screening for Fabry disease (FD) in high risk populations yields a significant number of individuals with novel, ultra rare genetic variants in the GLA gene, largely without classic manifestations of FD. These variants often have significant residual α-galactosidase A activity. The establishment of the pathogenic character of previously unknown or rare variants is challenging but necessary to guide therapeutic decisions. OBJECTIVES: To present 2 cases of non-classical presentations of FD with renal involvement as well as to discuss the importance of high risk population screenings for FD. RESULTS: Our patients with non-classical variants were diagnosed through FD screenings in dialysis units. However, organ damage was not limited to kidneys, since LVH, vertebrobasilar dolichoectasia and cornea verticillata were also present. Lyso-Gb3 concentrations in plasma were in the pathologic range, compatible with late onset FD. Structural studies and in silico analysis of p.(Cys174Gly) and p.(Arg363His), employing different tools, suggest that enzyme destabilization and possibly aggregation could play a role in organ damage. CONCLUSIONS: Screening programs for FD in high risk populations are important as FD is a treatable multisystemic disease which is frequently overlooked in patients who present without classical manifestations.
RESUMO
Population-based surveillance and a case-control study were conducted in Abancay, Peru, to estimate the burden of disease and to determine risk factors for sporadic lymphocutaneous sporotrichosis (LS). Laboratory records from local hospitals were reviewed for the years of 1997 and 1998, and prospective surveillance was conducted for the period of September 1998 through September 1999. A case-control study was conducted with 2 matched control subjects per case patient. The mean annual incidence was 98 cases per 100,000 persons. Children had an incidence 3 times higher than that for adults and were more likely to have LS lesions on the face and neck. Identified risk factors included owning a cat, playing in crop fields, having a dirt floor in the house, working mainly outdoors, and having a ceiling made of raw wood or conditions associated with a lower socioeconomic status. Decreased environmental exposure, such wearing protective clothing during construction activities for adults or limiting contact with cats and soil for children, and improvements in living spaces may decrease the incidence of LS.
Assuntos
Doenças Endêmicas , Vigilância da População , Esporotricose/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Análise Multivariada , Peru/epidemiologia , Fatores de RiscoRESUMO
We describe the first human case of lobomycosis caused by Lacazia loboi in a 42-year-old white male resident of Georgia. The patient had traveled to Venezuela 7 years earlier, where he had planned to rappel down Angel Falls in Canaima. Although he never actually rappelled the falls, he did walk under the falls at least three times, exposing himself to the high water pressures of the falls. He noticed a small pustule with surrounding erythema developing on the skin of his right chest wall. The lesion gradually increased in size and had an appearance of a keloid. For cosmetic reasons, the patient sought medical treatment to remove the lesion. After an uncomplicated excision of the lesion, the patient recovered completely. The excised tissue was fixed in formalin for pathologic examination. Tissue sections stained by hematoxylin and eosin, periodic acid-Schiff stain, and Gomori methenamine silver stain procedures showed numerous histiocytes, multinucleated giant cells, and numerous globose or subglobose, lemon-shaped cells producing multiple blastoconidia connected by narrow tube-like connectors and catenate chains of various lengths characteristic of L. loboi.