Analysis of gene mutations and clinical manifestations in 20 patients with glycogen storage disease type Ia

Abstract

Objective To investigate the glucose-6-phosphatese catalytic(G6PC) unit G6PC gene mutations in patients with liver glycogen storage disease(LGSD), and to discuss the relationship of glycogen storage disease type Ⅰa(GSDⅠa) genotype and phenotype. Methods According to clinical manifestations, laboratory tests and glucagon test results, 48 patients suspected as LGSD were selected in this research.By using PCR combined with direct DNA sequencing, the entire coding region of the G6PC gene was screened.Fifty healthy children were also investigated as control group.The species homology was analyzed by DNAMAN software to investigate gene conservatism. Results Eight types of G6PC gene mutations were detected in 20 cases of the 48 patients(41.67 %, 20/48 cases), which were c. 648G>T, p.R83H, p.H119L, p.L173P, p.I341N, c.260-262delGGinsA, p.C109Y and c. 260-262delGGinsA.Among which, c.648G>T and p. R83H were the common gene mutations in this study, their mutations frequency were 37.50% and 22.50%, respectively.p.C109Y and c. 260-262delGGinsA were novel mutations.All patients with different mutations had the same growth retardation, hypoglycemia, hepatomegaly, hyperlipidemia, lactic acidemia.Eighty-eight point twenty-four percent(15/17 cases) patients were hypoglycemia when fasted for 6 hours.The low blood sugar in 82.35%(14/17 cases) patients was no responsive to glucagon injection. Conclusions In this study, it revealed that c. 648G>T and p. R83H were the most common mutations in our patients.Two new pathogenic mutation types were found, which were p. C109Y and c. 260-262delGGinsA.The patients with different genotypes showed the same typical clinical manifestations. Key words: Glycogen storage disease type Ⅰa; Glucose-6-phosphatase; Gene mutation