Hepatic Manifestations in Glycogen Storage Disease Type III
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Purpose of Review
Glycogen storage disease type III (GSD III) is an orphan disease that mainly affects the liver, heart, and skeletal muscles. It is caused by the deficiency of glycogen debranching enzyme (GDE), resulting in accumulation of glycogen (limit dextrin) primarily in the cytoplasm. With an increase in life expectancy in patients and advances in research, long-term hepatic manifestations are being recognized. This review examines our understanding of the natural history of the hepatic manifestations of GSD III and the importance of developing definitive therapies.
Animal models have shown specific trends in biochemical and histological features such as changes in liver enzymes and progressive hepatic fibrosis, with increasing age. In our clinical experience, patients with GSD III show similar trends.
Our review highlights (a) hepatic manifestations in GSD III, (b) the natural history, (c) existing animal models, and (d) current research on therapeutic approaches.
KeywordsGlycogen storage disease III AGL gene variants Glycogen debranching enzyme deficiency Hepatic manifestations Liver fibrosis
We thank Dr. Carine Halaby for editing a draft of the manuscript and for providing help with literature searches in GSD III.
Compliance with Ethical Standards
Conflict of Interest
P.S.K. reports receiving research grant from Genzyme. B.S. reports receiving research grant from Roivant Sciences. P.S.K. and B.S. are listed as inventors on a Duke University patent for the use of rhGAA in the treatment of GSD III and other GSDs excluding GSD II. To date, neither Duke University nor the inventors has received any money from the commercialization of rights associated with this patent. The other authors (A.K. and S.A.) declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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