Glycogen storage disease type VI: clinical course and molecular background
Glycogen storage disease type VI (GSD-VI; also known as Hers disease, liver phosphorylase deficiency) is caused by mutations in the gene coding for glycogen phosphorylase (PYGL) leading to a defect in the degradation of glycogen. Since there are only about 40 patients described in literature, our knowledge about the course of the disease is limited. In order to evaluate the long-term outcome of patients with GSD-VI, an observational retrospective case study of six patients was performed at the University Children’s Hospital Zurich. The introduction of small, frequent meals as well as cornstarch has led to normal growth in all patients and to normalization of liver transaminases in most patients. After starting the dietary regimen, there were no signs of hypoglycemia. However, three of six patients showed persistent elevation of triglycerides. Further, we identified four novel pathogenic PYGL mutations and describe here their highly variable impact on phosphorylase function.
What is Known:
• Glycogen storage disease type VI (GSD-VI) is a metabolic disorder causing a defect in glycogen degradation. Dietary treatment normally leads to metabolic stability and prevention of hypoglycemia.
• However, our knowledge about the natural course of patients with GSD-VI is limited.
What is New:
• While outcome was overall excellent in all patients, half of the patients showed persistent hypertriglyceridemia even after initiating treatment.
• Molecular genetics added important information for the understanding of the clinical variability in this disease.
KeywordsGlycogen storage disease type VI Long-term outcome Hypertriglyceridemia Molecular genetic background Phosphorylase
Glycogen storage disease
Glycogen storage disease type VI
Red blood cells
We would like to thank the families for their willingness to be part of this project.
Tim Aeppli and Johannes Häberle designed the study. Tim Aeppli collected the data, carried out the analysis, created the tables, and drafted the manuscript. Daisy Rymen analyzed the different PYGL mutations and wrote the “Diagnostic workup” section. Peter Bode performed the histological workup. Gabriella Allegri created the graphs. All the authors reviewed and revised the manuscript draft and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval and consent
We received parental consent for publication of patient-related data, which is commensurate to IRB approval according to local regulations.
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