Background and aims: A few cases are reported of liver neoplasms observed in patients with glycogen storage disease type 1a (GSD1a). Genetic analysis was carried out in adult Japanese patients with GSD1a and their family members, and hepatic tumors were also investigated in these patients.
Methods: DNA was extracted from the peripheral blood lymphocytes of 20 adult patients with GSD1a and 21 family members, and mutations were detected based on the differences in the polymerase chain reaction (PCR) products of the glucose-6-phosphatase (G6Pase) gene shown by single-strand conformation polymorphism (SSCP) analysis. Actual mutations were confirmed by direct sequencing. The relationship between the occurrence of liver tumors and the clinical characteristics of the patients was also investigated.
Results: Nineteen of the 20 patients were homozygous for the G727T mutation and one was a compound heterozygote for G727T plus G327A mutations. All of the 19 homozygotes for G727T had hepatomegaly, three had hepatocellular carcinoma, one had cholangiocellular carcinoma, and seven had hepatic adenoma. There were no differences between the tumor and non-tumor groups with respect to laboratory biochemical data (P > 0.05). The mean age of G727T homozygotes with hepatocellular carcinoma was 48.3 years, and that of those with hepatic adenoma was approximately 20 years younger.
Conclusion: The G727T mutation seems to be common among Japanese patients with GSD1a, and the discovery of one heterozygote with a combination of G727T and G327A mutations (the latter mutation is common among Chinese) by the use of polymerase chain reaction-single strand conformation polymorphism analysis gave further insight into Japanese ancestry. This is the first study of liver tumors in a large group of adult GSD1a patients with the G727T mutation. As most of the patients in our series are free from other chronic liver diseases such as viral hepatitis, other genetic and/or acquired factors may have influence on the sequel to this metabolic disease.