Review for 10.1186/s12876-021-01749-x (2021)

Reviewer’s report
Title: 
Successful Treatment of Infantile Oxysterol 7
α
-hydroxylase Deficiency
with Oral Chenodeoxycholic Acid
Version: 
0 
Date: 
27 Nov 2020
Reviewer's report:
Major Comments
Abstract and Background: "Most patients with CYP7B1 deficiency succumb to
liver failure in early life." There are more reports of SPG5 due to CYP7B1
mutations than there are reports of liver failure due to CYP7B1 mutations. So I
think this should read, "Most reported patients with CYP7B1 mutations
presenting with liver disease in infancy have died of liver failure".
Page 3 and Figure 2. Urinary bile acid profiles. Interpretation of the spectra
would have been greatly enhanced by daughter ion scans. There is a very
prominent peak in the first spectrum with mass/charge ratio 480. While this
could be 
a glycine-conjugated tetrahydroxycholanoic acid (seen frequently in
infants with liver disease and/or on ursodeoxycholic acid), it could also be
taurine-conjugated 3beta-hydroxy-5-cholenoic acid and this was the largest peak
described for the 
CYP7B1 deficient patient 
in the Dai et al. paper. In the former
case the major daughter ion would be m/z 74; in the latter case, m/z 80. Bile acid
identities could also have been clarified by GC-MS
In the interpretation of subsequent urine bile acid analyses, a peak with
mass/charge ratio 510 
is interpreted as indicating the presence of glycine- and
sulphate- conjugated 3beta-hydroxy-5-cholenoic acid, however, children with
severe liver disease often excrete taurine-conjugated 7alpha,12alpha,3-oxo-4-
cholenoic acid which also has a mass/charge ratio of 510. These two bile acids
can again be distinguished by their principal daughter ions so tandem MS
analysis (or GC-MS) would have been helpful.
"Consequently, repeat testing combined with genetic analysis is usually
recommended in cases like this to definitively confirm the diagnosis". It is also
important to point out how difficult it is to interpret spectra from children who
are being treated with ursodeoxycholic acid and wherever possible samples
should be sent for analysis at least 2 weeks after stopping this treatment.
Minor Comments
Spaces between words missing: e.g. P2 "inCYP7B1(Fig.1)"
P2 "Physical examinations showed jaundice, groan and shortness of breath". I
am not sure what the authors are attempting to say with the word "groan".
Perhaps "groaning"; 
a sick child may groan but it is not a particularly useful sign.
Perhaps "grunting"; in the first few weeks of life he/she may grunt - a sign of
expiration against a partially closed glottis that indicates respiratory distress.
Also "shortness of breath" is a subjective sign that can be described by adults; for
infants it is more usual to describe what can be objectively observed e.g.
tachypnoea, grunting, recession, cyanosis.
"The laboratory investigations showed elevated levels of … 
total bile acids
(TBA), …" It is important to state the method being used for TBA analysis. It
was probably a method based on 3alpha-hydroxysteroid dehydrogenase; this
gives a low value for many children with inborn errors of bile acid synthesis
because synthesis of 3alpha-hydroxy bile acids is reduced. 
P4. "Recent lumbar magnetic resonance imaging (MRI) suggested physiological
bending become straightening..". 
I don't know what this means; the English
requires attention.
Figure 3. Arrows indicating the features described would help readers without
expertise in brain MRI interpretation.
P4. "By contrast, the acidic pathway is initiated by 27-hydroxylation of
cholesterol followed by 7
α
-hydroxylation of the monohydroxylated
intermediates 3
β
-hydroxy-5-cholestenoic and 3
β
-hydroxy-5-cholenoic acids to
yield CDCA [2, 13, 14], a reaction that is catalyzed by oxysterol-7
α
-hydroxylase
(CYP7B1)". Suggest "By contrast, the acidic pathway is initiated by 27-
hydroxylation of cholesterol followed by 7
α
-hydroxylation of the
monohydroxylated intermediates 3
β
-hydroxy-5-cholestenoic and 3
β
-hydroxy-5-
cholenoic acids, a reaction that is catalyzed by oxysterol-7
α
-hydroxylase
(CYP7B1); this pathway leads ultimately to 
production of CDCA [2, 13, 14]"
P5. "CDCA suppressed sterol 27-hydrolylase" > 27-hydroxylase
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