Investigations Into Glycogen Storage Disease â… a Diagnosed In Adult

Objective Mutations in the glucose-6-phosphatase (G6PC) gene are responsible for glycogen storage disease type Ia (GSD Ia). Nowadays, DNA sequencing analysis technology has been widely used to diagnose genetic disease including GSD Ia. Biopsies of the liver are not necessary when GSD Ia is suspected. But, there are still some adults with GSD Ia can’t be diagnosed because of novel type mutation. By genotype analysis of the affected pedigree, we identified a novel type mutation in a Chinese patient with GSD Ia.Methods Prior to a histological pathological analysis of a fresh liver specimen, a suspicious diagnosis of GSD Ia was made by clinical and laboratory presentations. Genomic DNA was isolated from EDTA blood. All the five exons and the flanking introns of the G6PC gene were amplified by polymerase chain reaction (PCR). Mutation analysis was performed for the coding region of G6PC gene using DNA sequencing and TaqMan gene expression assay was used to further confirm the novel mutation.Results Combining the two approaches, we were able to detect mutations in all of the patient’s alleles, showing 100% sensitivity. Family studies revealed that the father was heterozygous for the C.311A>T mutation and the mother was confirmed to be heterozygous for the C.648G>T mutation. The analyses revealed that the patient has compound heterozygotes with a novel missense mutation of c.311 A>T derived from his father, and c.648G>T mutation derived from his mother.Conclusions Numerous assumptions support that c.311A>T is a disease-causing mutation. The missense mutation leads to the substitution of a leucine (L) for a glutamine (Q) at codon 104. Such a change could affect G6PC activity and stability. Our research expands the spectrum of G6PC gene mutation in China. This type of patient, who can survive to adulthood without any treatment, is certainly a mild phenotype. In mild GSD la patients, the risks and benefits of organ transplantation or future gene therapy should be seriously considered. The genotype-phenotype correlation in GSD la is an important area that requires further research.Objective To investigate the molecular genetic background of a pedigree with glycogen storage disease la (GSD Ia) and focus on secondary osteoporosis caused by the disease.Methods The proband and her younger brother underwent bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DEXA) for spine, left forearm and hip. DNA was extracted from the peripheral blood of the proband and her father and mother. All the five exons and the flanking introns of the glucose-6-phosphatease gene were amplified by polymerase chain reaction. Actual mutations were confirmed by direct sequencing.Results Spine BMD and left hip BMD of the patients were below the expected range for age. Left forearm BMD of the provand’s younger brother was below the expected range for age. The DNA-based analysis revealed that the proband was homozygous for the c.648G>T mutation. The provand’s father, as well as her mother was heterozygous for the c.648G>T mutation.Conclusion GSD Ia is an extremely rare cause of secondary osteoporosis in adult. Adult who has unexplained osteoporosis, hepatomegaly, hyperlipemia, hyperuricemia and a marked increase of blood lactic acid concentration should be screened for GSD. The pathogenesis and the genotype-phenotype correlation require further research.