Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Liver phosphorylase deficiency (glycogen storage disease VI, Hers disease)

William J Craigen, MD, PhD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


There are a number of inborn errors of glycogen metabolism that result from mutations in genes for virtually all of the proteins involved in glycogen synthesis, degradation, or regulation. Those disorders that result in abnormal storage of glycogen are known as glycogen storage diseases (GSDs). They have largely been categorized by number according to the chronology of recognition of the responsible enzyme defect (table 1). Liver phosphorylase deficiency (GSD VI, MIM #232700), also known as Hers disease, is usually a mild form of glycogenosis; however, severe hepatomegaly and recurrent severe hypoglycemia have been described [1]. It is due to deficiency of the liver isoform of phosphorylase.

Liver phosphorylase deficiency is reviewed here. Other GSDs are reviewed separately.


Glycogen is the stored form of glucose and serves as a buffer for glucose needs. Glycogen is formed in periods of dietary carbohydrate loading and broken down when glucose demand is high or dietary availability is low (figure 1).

Glycogen is most abundant in liver and muscle, which are most affected by disorders of glycogen metabolism. The physiologic importance of a given enzyme in liver and muscle determines the clinical manifestations of the disease. The main role of glycogen in the liver is to store glucose for release to tissues that are unable to synthesize significant amounts during fasting. The major manifestations of disorders of glycogen metabolism affecting the liver are hypoglycemia and hepatomegaly. (See "Physiologic response to hypoglycemia in normal subjects and patients with diabetes mellitus".)

A more extensive overview of GSD is presented separately. (See "Overview of inherited disorders of glucose and glycogen metabolism".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Oct 2017. | This topic last updated: Jun 24, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. GeneReviews: Glycogen Storage Disease Type VI http://www.ncbi.nlm.nih.gov.ezp-prod1.hul.harvard.edu/books/NBK5941/?&log$=disease6_name (Accessed on July 13, 2011).
  2. Chang S, Rosenberg MJ, Morton H, et al. Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI. Hum Mol Genet 1998; 7:865.
  3. Burwinkel B, Bakker HD, Herschkovitz E, et al. Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI. Am J Hum Genet 1998; 62:785.
  4. Tang NL, Hui J, Young E, et al. A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity. Mol Genet Metab 2003; 79:142.
  5. Beauchamp NJ, Taybert J, Champion MP, et al. High frequency of missense mutations in glycogen storage disease type VI. J Inherit Metab Dis 2007; 30:722.
  6. Chen YT. Glycogen storage diseases. In: The metabolic and molecular bases of inherited disease, 8th ed, Scriver CR, Beaudet AL, Sly WS, Valle D (Eds), McGraw Hill, New York 2001.
  7. Roscher A, Patel J, Hewson S, et al. The natural history of glycogen storage disease types VI and IX: Long-term outcome from the largest metabolic center in Canada. Mol Genet Metab 2014; 113:171.
  8. Paesold-Burda P, Baumgartner MR, Santer R, et al. Elevated serum biotinidase activity in hepatic glycogen storage disorders--a convenient biomarker. J Inherit Metab Dis 2007; 30:896.
  9. Davit-Spraul A, Piraud M, Dobbelaere D, et al. Liver glycogen storage diseases due to phosphorylase system deficiencies: diagnosis thanks to non invasive blood enzymatic and molecular studies. Mol Genet Metab 2011; 104:137.
  10. Ogawa A, Ogawa E, Yamamoto S, et al. Case of glycogen storage disease type VI (phosphorylase deficiency) complicated by focal nodular hyperplasia. Pediatr Int 2010; 52:e150.
  11. Manzia TM, Angelico R, Toti L, et al. Glycogen storage disease type Ia and VI associated with hepatocellular carcinoma: two case reports. Transplant Proc 2011; 43:1181.