Glycogen storage disease type Ia: molecular study in Brazilian patients

Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for gl ycogen storage disease type Ia (GSDIa). This disease is characterized by gr owth retardation, hepatomegaly, hypoglycemia, hyperlipidemia, and lactic ac idosis. In this study, we report mutations in the G6Pase gene in 8 of 25 Br azilian 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 (5 7.14%) mutant alleles. A 1176 single-nucleotide polymorphism and two intron ic mutations (IVS3-58T>A and IVS4+10G>A) were also analyzed. We used the mi nigene strategy in order to verify the effect of these intronic mutations o n the splicing mechanism. This study emphasizes that molecular genetic anal ysis is a reliable and convenient alternative to the assay of enzyme activi ty in a fresh liver biopsy specimen for dianosing GSDIa.