RESUMO
Repeated evaluation of biotinidase (BTD) activity was carried out for a long-term follow-up in patients with hepatic glycogen storage diseases (GSDs). The results indicated inter-intra variability among the GSD-Ia, GSD-III and GSD-IX patients. In addition, a c.1330G>C transversion in the BTD gene, resulting in a p.Asp444His substitution was detected in one allele of a GSD-Ia patient with sustained normal enzyme activity. Thus far, it is necessary to be cautious in the interpretation of the results of BTD activity as a presumptive GSD diagnostic element. It is not known why plasma BTD activity increases in GSDs patients, or the clinical importance of the increment. When viewed from a global perspective, there are some lines of biotin biology that could indicate a relationship between BTD´s behavior and GSDs.
Assuntos
Biotinidase/sangue , Doença de Depósito de Glicogênio/enzimologia , Fígado/enzimologia , Argentina , Biomarcadores/sangue , Biotinidase/genética , Estudos de Casos e Controles , Análise Mutacional de DNA , Genótipo , Doença de Depósito de Glicogênio/sangue , Doença de Depósito de Glicogênio/diagnóstico , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio Tipo I/enzimologia , Doença de Depósito de Glicogênio Tipo III/enzimologia , Humanos , Mutação , Fenótipo , Regulação para CimaRESUMO
Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen storage disease type Ia (GSDIa). This disease is characterized by growth retardation, hepatomegaly, hypoglycemia, hyperlipidemia, and lactic acidosis. In this study, we report mutations in the G6Pase gene in 8 of 25 Brazilian patients with clinical symptoms of GSDIa. Five previously described mutations (R83C, Q347X, V338F, D38V, and G68R) were detected. The two most common mutations identified were R83C and Q347X, accounting for 8 of 14 (57.14%) mutant alleles. A 1,176 single-nucleotide polymorphism and two intronic mutations (IVS3-58T>A and IVS4+10G>A) were also analyzed. We used the minigene strategy in order to verify the effect of these intronic mutations on the splicing mechanism. This study emphasizes that molecular genetic analysis is a reliable and convenient alternative to the assay of enzyme activity in a fresh liver biopsy specimen for diagnosing GSDIa.
Assuntos
Glucose-6-Fosfatase/genética , Doença de Depósito de Glicogênio Tipo I/enzimologia , Doença de Depósito de Glicogênio Tipo I/genética , Mutação , Alelos , Sequência de Bases , Brasil , Análise Mutacional de DNA , Primers do DNA/genética , Frequência do Gene , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Humanos , Íntrons , Mutação Puntual , Polimorfismo de Nucleotídeo ÚnicoRESUMO
We report 2 patients with atypical glycogen storage disease type Ib without neutropenia or infectious complications. Neither patient was deficient in hepatic glucose-6-phosphatase activities in microsome-disrupted homogenates; both had mutations in the glucose-6-phosphate transporter gene, suggesting an allelic variant of glycogen storage disease type Ib.