Liver fibrosis during clinical ascertainment of glycogen storage disease type III: a need for improved and systematic monitoring

Genet Med. 2019 Dec;21(12):2686-2694. doi: 10.1038/s41436-019-0561-7. Epub 2019 Jul 2.


Purpose: In glycogen storage disease type III (GSD III), liver aminotransferases tend to normalize with age giving an impression that hepatic manifestations improve with age. However, despite dietary treatment, long-term liver complications emerge. We present a GSD III liver natural history study in children to better understand changes in hepatic parameters with age.

Methods: We reviewed clinical, biochemical, histological, and radiological data in pediatric patients with GSD III, and performed a literature review of GSD III hepatic findings.

Results: Twenty-six patients (median age 12.5 years, range 2-22) with GSD IIIa (n = 23) and IIIb (n = 3) were enrolled in the study. Six of seven pediatric patients showed severe fibrosis on liver biopsy (median [range] age: 1.25 [0.75-7] years). Markers of liver injury (aminotransferases), dysfunction (cholesterol, triglycerides), and glycogen storage (glucose tetrasaccharide, Glc4) were elevated at an early age, and decreased significantly thereafter (p < 0.001). Creatine phosphokinase was also elevated with no significant correlation with age (p = 0.4).

Conclusion: Liver fibrosis can occur at an early age, and may explain the decrease in aminotransferases and Glc4 with age. Our data outlines the need for systematic follow-up and specific biochemical and radiological tools to monitor the silent course of the liver disease process.

Keywords: GSD III liver; cirrhosis; hepatocellular fibrosis; urinary glucose tetrasaccharide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers
  • Child
  • Child, Preschool
  • Cholesterol / analysis
  • Cholesterol / metabolism
  • Female
  • Glycogen
  • Glycogen Storage Disease / pathology
  • Glycogen Storage Disease Type I / pathology
  • Glycogen Storage Disease Type III / metabolism
  • Glycogen Storage Disease Type III / pathology*
  • Humans
  • Liver / pathology
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology*
  • Liver Diseases
  • Male
  • Oligosaccharides / analysis
  • Oligosaccharides / metabolism
  • Transaminases / analysis
  • Transaminases / metabolism
  • Triglycerides / analysis
  • Triglycerides / metabolism
  • Young Adult


  • Biomarkers
  • Oligosaccharides
  • Triglycerides
  • glucose tetrasaccharide
  • Glycogen
  • Cholesterol
  • Transaminases

Supplementary concepts

  • Glycogen Storage Disease IIIA