RESUMO
The urea cycle is a metabolic pathway for the disposal of excess nitrogen, which arises primarily as ammonia. Nitrogen is essential for growth and life-maintenance, but excessive ammonia leads to life-threatening conditions. The urea cycle disorders (UCDs) comprise diseases presenting with hyperammonemia that arise in either the neonatal period (about 50% of cases) or later. Congenital defects of the enzymes or transporters of the urea cycle cause the disease. This cycle utilizes five enzymes, two of which, carbamoylphosphate synthetase 1 and ornithine transcarbamylase are present in the mitochondrial matrix, whereas the others (argininosuccinate synthetase, argininosuccinate lyase and arginase 1) are present in the cytoplasm. In addition, N-acetylglutamate synthase and at least two transporter proteins are essential to urea cycle function. Severity and age of onset depend on residual enzyme or transporter function and are related to the respective gene mutations. The strategy for therapy is to prevent the irreversible toxicity of high-ammonia exposure to the brain. The pathogenesis and natural course are poorly understood because of the rarity of the disease, so an international registry system and novel clinical trials are much needed. We review here the current concepts of the pathogenesis, diagnostics, including genetics and treatment of UCDs.
Assuntos
Arginase , Encéfalo/enzimologia , Carbamoil-Fosfato Sintase (Amônia) , Mutação , Ornitina Carbamoiltransferase , Distúrbios Congênitos do Ciclo da Ureia , Arginase/genética , Arginase/metabolismo , Encéfalo/patologia , Carbamoil-Fosfato Sintase (Amônia)/genética , Carbamoil-Fosfato Sintase (Amônia)/metabolismo , Humanos , Ornitina Carbamoiltransferase/genética , Ornitina Carbamoiltransferase/metabolismo , Distúrbios Congênitos do Ciclo da Ureia/classificação , Distúrbios Congênitos do Ciclo da Ureia/enzimologia , Distúrbios Congênitos do Ciclo da Ureia/genética , Distúrbios Congênitos do Ciclo da Ureia/terapiaRESUMO
Semantic interoperability requires consistent use of controlled terminologies. However, non-terminology experts (although perhaps experts in a particular domain) are prone to produce variant coding. We examine this problem by investigating SNOMED CT coding variation for other findings reported on case report forms from a clinical research study on urea cycle disorders. The natural language findings from the forms were normalized, and the associated SNOMED CT concept descriptions were compared. The subset of normalized strings associated with two different concept descriptions were further compared to determine the relationship among the associated SNOMED CT concepts. We found 45% of the concept description pairs were associated with two hierarchically related concepts or with the same concept, while 55% were associated with two unrelated concepts. Clearer guidelines for use of SNOMED CT in particular contexts, or structured data entry tools tailored to the needs of non-expert coders, are needed to better manage coding variation.
