Genetics of Glycogen Storage Disease Type VI (Hers Disease) Clinical Presentation

Updated: Jun 13, 2018
  • Author: Anna V Blenda, PhD; Chief Editor: Maria Descartes, MD  more...
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The most common presentation of glycogen storage disease type VI (GSD VI), also known as Hers disease, is in children aged 1-5 years who have a history of protuberant abdomen, growth retardation, and slight delay in motor milestones. These children may also have a history of mild fasting hypoglycemia. Some individuals with GSD VI remain asymptomatic, and routine physical examination reveals hepatomegaly.

A 2003 case report described a 9-year-old boy diagnosed with GSD VI who had short stature and hepatomegaly. [11] Notably, this patient did not show fasting hypoglycemia, and DNA sequencing indicated a missense mutation in exon 6 of the PYGL gene.

In 2017, a child from India who presented with hepatomegaly, short stature, and elevated levels of transaminases was diagnosed with GSD VI at age 2.5 years. [12] The diagnosis of GSD VI was confirmed via next-generation sequencing (NGS), which uncovered a nonsense mutation in exon 11 of the PYGL gene that had not previously been reported. [12]

A 2015 report described a 3-year-old white girl diagnosed with GSD VI who presented with recurrent ketotic hypoglycemia but no hepatomegaly. [13]







Although children with GSD VI may have growth delay and short stature, adolescents and adults with the condition often have normal stature. The abdomen of a child with GSD VI usually protrudes, and abdominal examination reveals hepatomegaly and increased liver span. In some cases, hepatomegaly may be massive. However, splenomegaly is always absent. Adults with GSD VI may have mild or no hepatomegaly. Delays in motor milestones may be noted in young children with GSD VI. In adolescents and adults with GSD VI, muscle strength and tone are usually normal. Neuropathy can be associated with the disease; two children with GSD VI were reported to have axonopathy. [14]



Classic GSD VI results from a primary deficiency of hepatic glycogen phosphorylase. The gene that encodes liver glycogen phosphorylase, PYGL, resides on chromosome 14q22.1. [15, 12]