Oral Manifestations in Patients with Glycogen Storage Disease: A Systematic Review of the Literature

Round 1

Reviewer 1 Report

Main question is addressed to review of the recent literature on the topic which is relevant and interesting. Research is quite original because such review articles on this topic is hard to find, literature is primarily based on the case reports. It adds a scientific value to the subject because this is well written review of the most recent literature published on the topic. Text is clear and easy to read, conclusions are consistent with evidence and arguments presented and they address the main question. As I already have mentioned authors themselves claim that it has some limitations, but it analyzes valuable data and deserve publication.

Author Response

Naples, 14.09.2020

 

Dear reviewer,

 

Thank you for your response and reviewers’ valuable suggestions on our manuscript entitled “Oral manifestations in patients with Glycogen Storage Disease: a systematic review of the literature.” 

Thank you again for the time and the attention paid to our work,

Best regards,

Alberta Lucchese

 

Reviewer 2 Report

Dear author, only a few spelling errors need to be changed. - Table 1. Missing the "m" for November. - The paragraph that goes from line 226 to 230. It is repetitive information. - In line 211 a parenthesis must be removed.

Author Response

Dear reviewer,

Thank you for your response and reviewers’ valuable suggestions on our manuscript entitled “Oral manifestations in patients with Glycogen Storage Disease: a systematic review of the literature.” We have modified the paper in response to the insightful reviewer comments. We have rewritten some sections of the manuscript, and we hope that this complies with the referee’s remarks. We have submitted the revised manuscript, with the changes in red text.

We will respond to the comments point-counterpoint.

Thank you again for the time and the attention paid to our work,

Best regards,

Alberta Lucchese

 

Reviewer comments:

Dear author, only a few spelling errors need to be changed.

• Table 1. Missing the "m" for November. - The paragraph that goes from line 226 to 230. It is repetitive information. - In line 211 a parenthesis must be removed.

Thanks for the suggestion. The paragraph that goes from lines 226 to 230 has been removed, and grammatical errors have been corrected. 

Reviewer 3 Report

Authors have analyzed the literature as a systematic review to describe various oral manifestations of GSD.

 

Introduction needs to be improved about why we should know about various oral manifestation and how it impacts clinical practice rather than statements like "Patients with GSD should not make excessive muscular efforts" which is irrelevant to the current topic.

Table 1 can be a supplemental file.

PRISMA table should be more detailed as to why studies were excluded.

 

Table 2 is exhaustive - recommend cut shorting the table or incorporate with table 4

Table 3 can be removed or used as supplemental table.

Page 14 line 132: Typo crohn's disease and not Chron's disease

Reference 13 had crohn's disease in which oral manifestations are well documented. This cannot be attributed to the GSD and is misleading. Suggest removing this.

Page 14 line 134 Kishnani et al in their study had beefy red tongue which is secondary to vitamin B 12 deficiency. Same comments as above. This is not related to GSD but to vitamin B12 deficiency and hence misleading. Suggest removing these.

Page 15 line 155 Gijt in their study noted there is no direct causation and so this should be removed.

 

Discussion : needs to be redone. Significance of oral manifestation in GSD should be discussed rather than describing various types of GSD and their clinical manifestations.

Repetition of sentences "the main critical issue of this systematic review..."

Although ROBIN-I tool was used,data from case reports are misleading or not accurately captured and interpreted in this systematic review and hence removing studies with a clear explanation for oral manifestation other than GSD would be more representative of the systematic review intended.

Author Response

Dear reviewer,

Thank you for your response and reviewers’ valuable suggestions on our manuscript entitled “Oral manifestations in patients with Glycogen Storage Disease: a systematic review of the literature.” We have modified the paper in response to the insightful reviewer comments. We have rewritten some sections of the manuscript, and we hope that this complies with the referee’s remarks. We have submitted the revised manuscript, with the changes in red text.

We will respond to the comments point-counterpoint.

Thank you again for the time and the attention paid to our work,

Best regards,

Alberta Lucchese

 

Reviewer comments:

• Introduction needs to be improved about why we should know about various oral manifestation and how it impacts clinical practice rather than statements like "Patients with GSD should not make excessive muscular efforts" which is irrelevant to the current topic.

Following the reviewer’s suggestions, the introduction has been improved, and the statement "Patients with GSD should not make excessive muscular efforts" has been removed.

• Table 1 can be a supplemental file.

Table 1 has been added as a supplement file, as suggested by the reviewer.

• PRISMA table should be more detailed as to why studies were excluded.

Thanks to the reviewer for the suggestion. The PRISMA table has been updated according to the recommendations of the referee.

• Table 2 is exhaustive - recommend cut shorting the table or incorporate with table 4

Table 4 has been removed, as suggested by the reviewer.

• Table 3 can be removed or used as supplemental table.

Table 3 has been removed and added to the supplement material.

• Page 14 line 132: Typo crohn's disease and not chron's disease. Reference 13 had crohn's disease in which oral manifestations are well documented. This cannot be attributed to the GSD and is misleading. Suggest removing this.

We appreciate the suggestion of the reviewer, and we removed the terms chron’s disease and substituted with IBD; moreover, the following phrase has been added to the discussion section:

“In some reported articles, GSD I is associated with other systemic diseases. In particular, the work of Dieckgraefe et al. [13] found a strong association between GSD Ib and inflammatory bowel disease (IBD). The Authors reported several intraoral manifestations that could be related to the IBD, in which the oral presentations are well documented, and therefore cannot be directly attributable to GSD. “

• Page 14 line 134 Kishnani et al in their study had beefy red tongue which is secondary to vitamin B 12 deficiency. Same comments as above. This is not related to GSD but to vitamin B12 deficiency and hence misleading. Suggest removing these.

Thanks for the suggestion. We modified the Discussion section, highlighting that oral lesions were related to the dietary regimen and the vitamin B12 deficiency rather than the GSD.

• Page 15 line 155 Gijt in their study noted there is no direct causation and so this should be removed.

Thanks for the valuable suggestion. Although we agreed with the reviewer that Gijt et al. at first failed to attribute gingival growth directly to glycogenosis, they provide hypotheses that deserve to be mentioned. To make this result clearer and more appropriate, the discussion section has been changed as follow:

“Curiously, a single case report reported a massive gingival overgrowth. Authors, even if unable to fully explain the oral manifestation, hypothesized that a mixture of chronic inflammation, dryness of the gingiva, and the slight glycogen accumulation in the fibroblasts might have performed a role in the etiology of the patient’s gingival overgrowth.”

• Discussion: needs to be redone. Significance of oral manifestation in GSD should be discussed rather than describing various types of GSD and their clinical manifestations.

Thanks for the suggestions. The Discussion section has been modified to improve the value of oral manifestations in GSD patients.

• Repetition of sentences "the main critical issue of this systematic review..."

Thanks for the hint. The paragraph that goes from line 226 to 230 has been removed.

• Although ROBIN-I tool was used, data from case reports are misleading or not accurately captured and interpreted in this systematic review and hence removing studies with a clear explanation for oral manifestation other than GSD would be more representative of the systematic review intended

Thanks for the precious suggestion. Paragraphs relating to studies that might seem misleading, e.g., as those by Gijt et al., Kishnani et al., Amaral et al., Dellinger et al., have been modified in the discussions and Table 2.

We want to thank the referee for the attention He dedicated to our work.

Reviewer 4 Report

This article is a systematic review of the literature regarding oral manifestations of glycogen storage disease.  The authors found 45 articles matching their criteria and provide a thorough overview of the data.  Overall, the article is well-written and suitable for publication in Applied Sciences following minor revisions.

 

Specific issues that should be addressed are the following:

 

Line 73:  should be ‘case reports’ not ‘case report’

 

Line 85:  should be “RoB”, not “Rob”

 

Lines 183-184:  This sentence is confusing and should be reworded.

 

Lines 206-211 and 225-230:  These two sentences are repeated, verbatim, in two spots.  I am guessing that this is an error and that these two sentences belong at the end of the Discussion section?

Author Response

Dear reviewer,

Thank you for your response and reviewers’ valuable suggestions on our manuscript entitled “Oral manifestations in patients with Glycogen Storage Disease: a systematic review of the literature.” We have modified the paper in response to the insightful reviewer comments. We have rewritten some sections of the manuscript, and we hope that this complies with the referee’s remarks. We have submitted the revised manuscript, with the changes in red text.

We will respond to the comments point-counterpoint.

Thank you again for the time and the attention paid to our work,

Best regards,

Alberta Lucchese

 

Reviewer comments:

This article is a systematic review of the literature regarding oral manifestations of glycogen storage disease. The authors found 45 articles matching their criteria and provide a thorough overview of the data. Overall, the article is well-written and suitable for publication in Applied Sciences following minor revisions.

Specific issues that should be addressed are the following:

• Line 73: should be ‘case reports’ not ‘case report’
• Line 85: should be “RoB”, not “Rob”

Thanks for the suggestion. The misspelled terms have been modified.

• Lines 183-184: This sentence is confusing and should be reworded.

This sentence has been deleted, and the discussion section has been modified.

• Lines 206-211 and 225-230: These two sentences are repeated, verbatim, in two spots. I am guessing that this is an error and that these two sentences belong at the end of the Discussion section?

Thanks for the appropriate suggestion. The paragraph that goes from line 226 to 230 has been removed.

We want to thank the referee for the attention He dedicated to our work.

Reviewer 5 Report

Authors presented review about oral manifestations in patients with GSD. They following the PRISMA and PICOS checklist and and registered review on PROSPERO. Article has no novelty, because in PubMed are many articles in this topic. It seems to me that it was a mistake to consider old works from the 1990s. In Abstract is nothing about oral manifestations - Authors should mention at least these most often described.

I think that some described manifestations, e.g. "high levels of plaque and calculus", can be not associated with GSD, but only with lack of oral hygiene. Should be given into consideration social status of persons. Also should be given, if e.g. absence of tooth # 47 in adult person is congenital or related to the removal of this tooth at a later date.

There are more inaccuracies at work that arise for a dentist. The authors should indicate whether the oral lesions in question are actually related to GSD. It is possible that many of them arose later and result from lack of hygiene, tooth extraction or other negligence. They include, among others presence of plaque and calculus, caries, abscesses, gingivitis and periodontitis.

Above issues should be thoroughly clarified and corrected by the authors, because in its present form the work cannot be published.

Author Response

Dear reviewer,

Thank you for your response and reviewers’ valuable suggestions on our manuscript entitled “Oral manifestations in patients with Glycogen Storage Disease: a systematic review of the literature.” We have modified the paper in response to the insightful reviewer comments. We have rewritten some sections of the manuscript, and we hope that this complies with the referee’s remarks. We have submitted the revised manuscript, with the changes in red text.

We will respond to the comments point-counterpoint.

Thank you again for the time and the attention paid to our work,

Best regards,

Alberta Lucchese

Reviewer comments:

 

Reviewer #5

 

Authors presented review about oral manifestations in patients with GSD. They following the PRISMA and PICOS checklist and and registered review on PROSPERO. Article has no novelty, because in PubMed are many articles in this topic. 

 

• It seems to me that it was a mistake to consider old works from the 1990s. 

 

We agreed with the reviewer that it should be preferable to consider the more recent studies when performing a systematic review. However, the 1990 articles were selected according to the PRISMA checklist.

 

• In Abstract is nothing about oral manifestations - Authors should mention at least these most often described.

 

Thanks for the precious suggestion. The abstract section has been modified, and the most described oral manifestation has been added. 

 

• I think that some described manifestations, e.g. "high levels of plaque and calculus", can be not associated with GSD, but only with lack of oral hygiene. Should be given into consideration social status of persons. 

 

Thanks for the precious hint. Regarding the accumulation of plaque and tartar, they have been considered clinical manifestations because they are linked to immunodeficiencies and the special diet followed by the patients, as debated in the Discussion section.

 

• Also, should be given, if e.g. absence of tooth # 47 in adult person is congenital or related to the removal of this tooth at a later date.

 

Thanks for the suggestion. We removed the suggested manifestations from the table and the text, leaving only the primary described manifestation, such as the Hyperplasic purplish lesion localized adjacent to the teeth 32, 33, and 34. 

 

• There are more inaccuracies at work that arise for a dentist. The authors should indicate whether the oral lesions in question are actually related to GSD. It is possible that many of them arose later and result from lack of hygiene, tooth extraction or other negligence. They include, among others presence of plaque and calculus, caries, abscesses, gingivitis and periodontitis.

 

Thanks for the suggestions. The Discussion section has been modified to clarify the value of plaque and calculus, caries, abscesses, gingivitis, and periodontitis in GSD patients.

 

We want to thank the referee for the attention He dedicated to our work.

Round 2

Reviewer 3 Report

Authors have modified the manuscripts and responded to most of the queries. Some misleading sentences were modified  appropriately. Kindly consider for publication.

Reviewer 5 Report

Authors corrected manuscript according to Reviewer suggestions. I accept all changes.