Content of review 1, reviewed on June 01, 2020

Clin Genetics_PNPO def review of 62 cases

The authors review 2 cases from their own center review and add another 60 identified in the literature for a comprehensive clinical and genetic characterization of PNPO deficiency, an important rare treatable inherited metabolic epilepsy which has an interesting history in relation to B6 dependency. Please address these issues:
1. The authors do not actually describe their own cases. Based on the Tables, it appears they already published one as: Alghamdi et al 2019: J Pediatr Epilepsy (although I could not identify this paper in PubMed). Based on a Google search, this was a single case report. Thus, it is unclear what the details are of the authors’ own cases. In any case, this paper is really a literature review and should be re-titled as search.
2. In the Tables, the reference Phillip et al 2012 appears to actually be Pearl et al 2013 as cited in the references.
3. It is surprising the authors do not describe the retinopathy described in Guerriero et al 2017, given their emphasis on the pleiotropic phenotype including extraneuronal manifestations in this review.
4. The condition is, strictly speaking, a dependency state on PLP, not a deficiency state. That is, this is not a dietary deficiency in the strict sense but instead a metabolic disorder due to an enzymatic deficiency. Thus, the Abstract (sentence 2) should correct this as being a dependency on PLP and not a deficiency of PLP. Along the same lines, in the Introduction (first paragraph), the deficiency in PNPO causes a dependency of PLP, not a “shortage” of PLP.
5. For the section 3.3, it is unclear why the subtitle is: Brain CSF analysis findings, instead of CSF analysis.
6. No PLP levels are discussed in the CSF findings; this is surprising and an important laboratory omission.
7. In Section 5. PNPO Deficiency Outcome, the groups A, B, and C are named but not defined. They should be explained here.

Source

    © 2020 the Reviewer.

Content of review 2, reviewed on August 06, 2020

The newly written yellow highlighted area at the end on hepatic toxicity of PLP is very confusing. The first "sentence" is only a phrase and not even a sentence. The closing statements are unclear whether elevated transminases were present before or after PLP was introduced. Please edit the newly written area carefully;.

Source

    © 2020 the Reviewer.

References

    Malak, A., A., B. F., Marwa, A., Nouran, A., Z., J. D., M., S. K., Bandar, A., T., A. S. 2021. Phenotypic and molecular spectrum of pyridoxamine-5 '-phosphate oxidase deficiency: A scoping review of 87 cases of pyridoxamine-5 '-phosphate oxidase deficiency. Clinical Genetics.