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Glycogen storage disease type VI: clinical course and molecular background

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Abstract

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.

Conclusions: After establishing the diagnosis, dietary treatment led to metabolic stability and to prevention of hypoglycemia. Molecular genetics added important information for the understanding of the clinical variability in this disease. While outcome was overall excellent in all patients, half of the patients showed persistent hypertriglyceridemia even after initiating treatment.

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.

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Abbreviations

ALT:

Alanine transaminase

AST:

Aspartate transaminase

BTN:

Biotinidase

DNA:

Deoxyribonucleic acid

EBV:

Epstein-Barr virus

f:

Female

GSD:

Glycogen storage disease

GSD-VI:

Glycogen storage disease type VI

HM:

Hepatomegaly

LE:

Liver enzymes

m:

Male

mRNA:

Messenger RNA

PBK:

Phosphorylase b-kinase

PYGL :

Glycogen phosphorylase

RBC:

Red blood cells

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Acknowledgments

We would like to thank the families for their willingness to be part of this project.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Diabetology, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Tim RJ Aeppli

  2. Division of Metabolism and Children’s Research Center, University Children’s Hospital Zurich, Steinwiesstrasse 75, 8032, Zurich, Switzerland

    Daisy Rymen, Gabriella Allegri & Johannes Häberle

  3. Institute of Pathology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland

    Peter K Bode

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  1. Tim RJ Aeppli
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  5. Johannes Häberle
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Contributions

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.

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Correspondence to Tim RJ Aeppli.

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We received parental consent for publication of patient-related data, which is commensurate to IRB approval according to local regulations.

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Aeppli, T.R., Rymen, D., Allegri, G. et al. Glycogen storage disease type VI: clinical course and molecular background. Eur J Pediatr 179, 405–413 (2020). https://doi.org/10.1007/s00431-019-03499-1

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  • DOI: https://doi.org/10.1007/s00431-019-03499-1

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