Glycogen storage disease (GSD) comprises a group of autosomal recessive disorders characterized by deficiency of the enzymes that regulate the synthesis or degradation of glycogen. Types Ia and Ib are the most prevalent; while the former is caused by deficiency of glucose-6-phosphatase (G6Pase), the latter is associated with impaired glucose-6-phosphate transporter, where the catalytic unit of G6Pase is located. Over 85 mutations have been reported since the cloning of G6PC and SLC37A4 genes. In this study, twelve unrelated patients with clinical symptoms suggestive of GSDIa and Ib were investigated by using genetic sequencing of G6PC and SLC37A4 genes, being three confirmed as having GSD Ia, and two with GSD Ib. In seven of these patients no mutations were detected in any of the genes. Five changes were detected in G6PC, including three known point mutations (p.G68R, p.R83C and p.Q347X) and two neutral mutations (c.432G > A and c.1176T > C). Four changes were found in SLC37A4: a known point mutation (p.G149E), a novel frameshift insertion (c.1338_1339insT), and two neutral mutations (c.1287G > A and c.1076-28C > T). The frequency of mutations in our population was similar to that observed in the literature, in which the mutation p.R83C is also the most frequent one. Analysis of both genes should be considered in the investigation of this condition. An alternative explanation to the negative results in this molecular study is the possibility of a misdiagnosis. Even with a careful evaluation based on laboratory and clinical findings, overlap with other types of GSD is possible, and further molecular studies should be indicated.
A púrpura trombocitopênica trombótica (PTT) é um distúrbio hematológico de baixa prevalência mundial a qual pode ser classificada, de acordo com a sua etiopatogênese, em congênita em caso de mutação genética, ou adquirida relacionada a um distúrbio autoimune com descontrole na produção de autoanticorpos. É caracterizado por trombocitopenia intensa decorrente da deficiência do organismo em sintetizar a enzima ADAMTS13, resultando em um acúmulo de glicoproteínas multiméricas do fator de von Willebrand (fvW). O fvW auxilia na manutenção da homeostase, desempenhando um papel fundamental no transporte molecular de proteínas solúveis e indução da agregação plaquetária. O aumento das glicoproteínas fvW resulta na agregação plaquetária intravascular e, consequentemente, em crises vaso oclusivas. Diante do grave curso da PTT e, por muitas vezes estar associada a outros distúrbios hematológicos, o diagnóstico precoce é essencial a fim de melhor definir o prognóstico e a terapêutica adequada. Entre os métodos de diagnóstico laboratorial, a técnica de citometria de fluxo tem mostrado melhor eficácia, devido a sua sensibilidade e especificidade. Nesse contexto, este trabalho teve por objetivo investigar a presença de ensaios clínicos os quais utilizam a citometria de fluxo como método preferencial para o diagnóstico da PTT a fim de realizar uma reflexão do impacto sobre o desfecho clínico da doença.
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