Ground Glass Hepatocellular Inclusions Caused by Disturbed Glycogen Metabolism in Three Children on Parenteral Nutrition

Brown, Rachel M.; Gray, George F.; Poulton, Kelvin; Wassmer, Evangaline; Gupte, Girish

doi:10.2350/08-09-0523.1

Cited by 8 publications

(5 citation statements)

References 3 publications

(10 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As far as we know, no systematic studies have been performed in extrahepatic sites in Tx patients with hepatocytic GGG. In a single case, investigations were performed to exclude a multisystem disease [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the literature, there are very few cases with more than one biopsy; the longest duration is 36 months [ 14 ]. Interestingly, in one child, there was a 40-month gap between the suspension of immunosuppressive drugs and the reinstitution of parenteral nutrition (PN) [ 17 ]. This would suggest that PN alone is a significant factor [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in one child, there was a 40-month gap between the suspension of immunosuppressive drugs and the reinstitution of parenteral nutrition (PN) [ 17 ]. This would suggest that PN alone is a significant factor [ 17 ]. In our series, four patients had been on both PN and immunosuppressive drugs.…”

Section: Discussionmentioning

confidence: 99%

“…In our study, the phenomenon has occurred in 17 out of 764 liver biopsies. All other studies report individual or group cases [ 14 , 15 , 16 , 17 ]. In conclusion, this study has proven that the GGG phenomenon reflects a disturbance of the glycogen metabolism and that the pathway recapitulates that of the PG body formation in SGSD.…”

Section: Discussionmentioning

confidence: 99%

“…However, GGG has also been reported in children under prolonged parenteral nutrition with or without immunosuppressive treatment [ 13 , 14 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Pathomorphogenesis of Glycogen-Ground Glass Hepatocytic Inclusions (Polyglucosan Bodies) in Children after Liver Transplantation

Callea

Francalanci

Grimaldi

et al. 2022

IJMS

View full text Add to dashboard Cite

Seventeen out of 764 liver biopsies from transplanted (Tx) livers in children showed glycogen-ground glass (GGG) hepatocytic inclusions. The inclusions were not present in pre-Tx or in the explanted or donor’s liver. Under the electron microscope (EM), the stored material within the cytosol appeared as non-membrane-bound aggregates of electron-lucent globoid or fibrillar granules, previously described as abnormally structured glycogen and identified as Polyglucosan bodies (PB). The appearance of GGG in our children was analogous to that of PB-GGG occurring in a number of congenital diseases due to gene mutations such as Lafora’s d., Andersen’s d., Adult Polyglucosan Body Disease and glycogenin deficiency. The same type of GGG was previously reported in the liver of patients undergoing transplants, immunosuppressive or antiblastic treatment. To explore the potential mechanism of GGG formation, we examined whether the drugs after whose treatment this phenomenon was observed could have a role. By carrying out molecular docking, we found that such drugs somehow present a high binding affinity for the active region of glycogenin, implicating that they can inactivate the protein, thus preventing its interaction with glycogen synthase (GS), as well as the maturation of the nascent glycogen towards gamma, beta or alfa glycogen granules. We could also demonstrate that PG inclusions consist of a complex of PAS positive material (glycogen) and glycogen-associated proteins, i.e., glicogenin-1 and -2 and ubiquitin. These features appear to be analogous to congenital GGG, suggesting that, in both cases, they result from the simultaneous dysregulation of glycogen synthesis and degradation. Drug-induced GGG appear to be toxic to the cell, despite their reversibility.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…However, GGG has also been reported in children under prolonged parenteral nutrition with or without immunosuppressive treatment [ 13 , 14 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations