Loading...
Publication
Biomarcadores nas doenças lisossomais de sobrecarga: o que são e o que nos dizem?
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 701.71 KB | Adobe PDF |
Advisor(s)
Abstract(s)
As Doenças Lisossomais de Sobrecarga (DLSs) são um conjunto de
patologias raras, crónicas, multissistémicas com modo de apresentação
e gravidade muito variáveis. No seu conjunto afetam aproximadamente
1:5000 nados vivos e são causadas pela acumulação de metabolitos não
degradados no interior do lisossoma. As esfingolipidoses são o grupo de
DLS com maior prevalência e incluem a doença de Gaucher, a doença de
Fabry e a doença de Niemann-Pick. Por vezes, parte do produto primário
de acumulação, através de uma reação de desacilação, é convertido na
respetiva base esfingoide, que se encontra bastante elevada em casos
de patologia. Em alguns doentes, estes compostos já se encontram
aumentados, mesmo antes do aparecimento dos primeiros sintomas. Os
tratamentos disponíveis para estas patologias (terapia de substituição
enzimática, terapia de redução de substrato de chaperones farmacológicos) conduzem a um decréscimo da concentração destas bases esfingoides, tornando o doseamento destes compostos útil também para aferir
a eficácia da terapêutica utilizada. Pela primeira vez em Portugal, é
disponibilizado o estudo destes biomarcadores para as DLSs, através
da tecnologia de espectrometria de massa em tandem (MS/MS). Os autores apresentam os resultados obtidos do doseamento destes lisolípidos
em diferentes doentes de DLSs, com a clara demonstração da especificidade destes biomarcadores, permitindo um diagnóstico atempado, um
melhor conhecimento da evolução da doença e monitorização da eficácia
do respetivo tratamento.
More than 50 inherited lysosomal storage disorders (LSDs) are presently known. They are a group of rare, multisystemic diseases with a variable presentation. Most are the result of an impairment of a catabolic enzyme, leading to the accumulation of the corresponding specific substrate(s) and subsequent pathology. LSDs are individually rare diseases, but as group they affect about 1 in 5,000 live births. The sphingolipidoses are due to deficiencies in the enzymes needed for lysosomal degradation of sphingolipid substrates and constitute the most prevalent group, where Gaucher, Fabry and Niemann-Pick diseases are included. In these disorders, the primary product of storage is deacylated into the respective sphingoid bases. In some cases, these products are already increased before the appearance of the first symptoms making them important for an early diagnosis. The available treatments for these pathologies can lead to the decrease of these sphingoid bases, raising the possibility of using them for treatment follow-up. For the first time in Portugal, it is available the study of several biomarkers for LSDs, through the technology of liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). The authors present the results of the measurement of these sphingoid bases in several LSD patients, showing a clear specificity of these biomarkers, allowing an early diagnosis, a better knowledge of the natural history of the disease and a evaluation of the efficacy of the treatment.
More than 50 inherited lysosomal storage disorders (LSDs) are presently known. They are a group of rare, multisystemic diseases with a variable presentation. Most are the result of an impairment of a catabolic enzyme, leading to the accumulation of the corresponding specific substrate(s) and subsequent pathology. LSDs are individually rare diseases, but as group they affect about 1 in 5,000 live births. The sphingolipidoses are due to deficiencies in the enzymes needed for lysosomal degradation of sphingolipid substrates and constitute the most prevalent group, where Gaucher, Fabry and Niemann-Pick diseases are included. In these disorders, the primary product of storage is deacylated into the respective sphingoid bases. In some cases, these products are already increased before the appearance of the first symptoms making them important for an early diagnosis. The available treatments for these pathologies can lead to the decrease of these sphingoid bases, raising the possibility of using them for treatment follow-up. For the first time in Portugal, it is available the study of several biomarkers for LSDs, through the technology of liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). The authors present the results of the measurement of these sphingoid bases in several LSD patients, showing a clear specificity of these biomarkers, allowing an early diagnosis, a better knowledge of the natural history of the disease and a evaluation of the efficacy of the treatment.
Description
Keywords
Doenças Lisossomais de Sobrecarga Doenças Hereditárias do Metabolismo Biomarcadores DLS Diagnóstico Conhecimento da Evolução da Doença Monitorização da Eficácia do Tratamento Doenças Genéticas Portugal
Pedagogical Context
Citation
Boletim Epidemiológico Observações. 2020 janeiro-abril;9(26):59-62
Publisher
Instituto Nacional de Saúde Doutor Ricardo Jorge, IP