Breath Analysis in Children with Ketogenic Glycogen Storage Diseases
, Praveen Kumar Conjeevaram Selvakumar 1, Xiaozhen Han 2, Xiaofeng Wang 2, David Grove 3, Adriano R. Tonelli 3,4, Raed A. Dweik 3,4, Laurie Minarich 5, Kadakkal Radhakrishnan 1 and Naim Alkhouri 1,6
José Javier Jareño-Esteban
Round 1
Reviewer 1 Report
1. Ketogenic glycogen storage disease involves the liver and kidney, resulting in hepatomegaly and splenomegaly, but there is no data statistics on hepatomegaly and splenomegaly in this study.
2. How long can VOCs reflect ketone metabolism？Different diet control groups can be considered.
Author Response
We thank the reviewer for his/her valuable comments. Below is our response to your comments highlighted in yellow
- Ketogenic glycogen storage disease involves the liver and kidney, resulting in hepatomegaly and splenomegaly, but there is no data statistics on hepatomegaly and splenomegaly in this study.
Answer: We reviewed physical exam of the patients and found that 6 patients out of 20 had palpable hepatomegaly on exam. no splenomegaly was palpable on exam. we added the following sentence to the 3.1. Participant characteristics: Palpable hepatomegaly was noted on exam in 6 patients and liver enzyme ALT had a wide range 10-409 U/L with a mean of 46.1 U/L
2. How long can VOCs reflect ketone metabolism？Different diet control groups can be considered.
Answer: We thank the reviewere for this great question. Unfortunately, we couldn't answer this question based on the data we have as we didn't record timing and content of the meals in relation to the sample collection. It will be a great direction for a future study
Also having a control group (could the patient him/herself) is a great idea.
in the light of this comment, we editted the limitations of the study (the last paragraph in the discussion section)
Author Response File: 
Author Response.docx
Reviewer 2 Report
But we considerer same recomendations in this abstrac
The authors used breath analysis for identify VOCS:
Is there correlation betwen VOCS with serum ketone (acetone, trimethylamine , pentane , 3 methiyhexane and carbon disulfide). We considerer wath trimethylamine and carbon disulfide wy dont now metabolic origen, because not recomend what utilised as biomarker screnning in breath samples.
Author Response
we thank the reviewer for his/her comments.
We re-reviewed the manuscript for English language and made several edits
As to the reviewer comment "Is there correlation betwen VOCS with serum ketone (acetone, trimethylamine , pentane , 3 methiyhexane and carbon disulfide). We considerer wath trimethylamine and carbon disulfide wy dont now metabolic origen, because not recomend what utilised as biomarker screnning in breath samples"
Answer: We proposed our explanation to the correlation between serum ketones and those VOC's. We agree that before considering them as "biomarkers" several future studies are needed before drawing those conclusions. We have this study is going to shed some light about those VOC's.
In light of this comment, we added the following to the discussion section "6) Finally, although several VOC’s showed correlation with serum ketones, similar studies are needed at a larger scale to further confirm this correlation"
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
I accept the author's explanation. This article explores the non-invasive detection of ketogenic glycogen storage diseases. Because a large number of patients are children, this non-invasive examination is very practical.
