The clinical and genetic analysis of glycogen storage disease type IV in 5 cases / 临床儿科杂志

Objective To investigate the characteristics of glycogen storage disease type IV (GSD IV) clinically, in laboratory tests and in gene mutation. Methods The clinical manifestations, biochemical indexes, activity of chitotriosidase, and the follow-up of the treatment in 5 cases of GSD IV were analyzed. Results Five patients (3 boys and 2 girls) aged 4 months - 5 years presented hepatosplenomegaly and elevated liver enzyme levels for 2 months at hospital visit. Two patients had motor developmental delay and weakness but their creatine kinase (CK) level were normal. Glycogen storage and liver fibrosis were observed in the liver biopsy in 4 patients. Target sequencing found that all 5 children carried the complex heterozygous mutation of the GBE1 gene with 2 reported mutations(p.R515C,p.R524Q)and 7 novel mutations.The novel mutation contains 5 missense mutations (p.I460T, p.F76S, p.F538V, p.L650R, p.W455R), one insertion mutations (c.141_142insGCGC), and one large fragment deletion (exon 3-7). Therefore, diagnosis of liver type of GSD IV was confirmed in those children. Two patients died of liver cirrhosis. The liver transplantation was performed due to liver cirrhosis in one patient whose chitotriosidase activity increased obviously before transplantation and decreased significantly after the transplantation and liver enzyme levels were returned to normal 4 months after transplantation. In the other two patients their growth and liver enzyme levels were normal;one had not received special treatments while the other was treated with raw corn starch and level of chitotriosidase was normal. Conclusions The clinical manifestations of GSD IV are heterogeneous. Target sequencing can be used for fast and noninvasive diagnosis of GSD IV. Chitotriosidase activity is useful in the prognosis assessment for GSD IV.

The study of expression and significance of GBE1 in hypoxic lung cancer based on GEO database / 安徽医科大学学报

Objective To investigate the expression of glucogen branching enzyme 1 (GBE1) in hypoxic lung cancer tissues and cells, to evaluate its significance for hypoxia tolerance in lung cancer and to explore its mechanism of apoptosis of lung cancer. Methods Data of 20 patients with hypoxic lung cancer and normoxia lung cancer tissue microarray were downloaded through the GEO database, GCBI was used to screen the differential genes for GO and KEGG pathway analysis. In vitro culture of A549 cells was cultured and transfected with siGEBl for knock down or GBE1 for overexpression. After hypoxia treatment, cell viability was analyzed using MTT assay. Western blot and real-time PCR were used to detect the expression of apoptosis-related genes. Results The data from 20 cases of lung cancer specimens showed that 206 genes displayed differences, and the GBE1 was the most significant, GO and KEGG pathway analysis found that the differential gene involved in cell cycle, cell metabolism and other multiple access. The expression of GBE1 in A549 cells after hypoxia treatment was significantly increased, and GBE1 could significantly enhance the expression of apoptosis-related genes in A549 cells after hypoxia treatment. Over-expression of GBE1 could inhibit the expression of apoptosis-related genes. Conclusion GBE1 may be a potential marker of hypoxia tolerance in lung cancer, this study provide a reference for further study of hypoxia tolerance mechanism of lung cancer.

Living Donor Liver Transplantation in a Korean Child with Glycogen Storage Disease Type IV and a GBE1 Mutation

Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease caused by a deficient glycogen branching enzyme (GBE), encoded by the GBE1 gene, resulting in the accumulation of abnormal glycogen deposits in the liver and other tissues. We treated a 20-month-old girl who presented with progressive liver cirrhosis and was diagnosed with GSD-IV, as confirmed by GBE1 gene mutation analysis, and underwent living related heterozygous donor liver transplantation. Direct sequencing of the GBE1 gene revealed that the patient was compound heterozygous for a known c.1571G>A (p.Gly264Glu) mutation a novel c.791G> A (Arg524Gln) mutation. This is the first report of a Korean patient with GSD-IV confirmed by mutation analysis, who was treated successfully by liver transplantation.