Review for 10.1186/1471-230X-12-119 (2012)

Reviewer's report
Title:Macro-AST: Misleading Finding in an Adolescent with MCAD-deficiency
Version: 1Date:22 May 2012
Reviewer: Devin Oglesbee
Reviewer's report:
Dear Authors,
You describe the incidental observation of a macro-AST in a sample from an
individual with MCAD deficiency. The elevated AST level was misinterpreted to
be indicative of liver dysfunction related to the genetic diagnosis. In turn, this
assumption lead to costly, and unnecessary evaluations for possible organ
dysfunction. In conclusion, you assert that consultation with a metabolic
specialist is paramount to assuring that individuals with MCAD deficiency are
provided proper care.
The case report that you describe has an interesting teaching point regarding
macro-enzymes.
I have a couple of specific corrections that should be made for clarity. Here is a
list for simplicity
1) MCAD deficiency is the come common inborn error of mitochondrial fatty acid
oxidation. Please make that distinction that it is a mitochondrial enzyme.
2) The factors attributing to the encephalopathy in MCAD deficiency is not
completely understood. It is presumed that toxic accumulation of fatty acid
metabolites proximal to the enzyme deficiency may add to the encephalopathy.
Thus, please add "possibly caused" to line 8, p.1.
3) Tandem-MS. Note that the common nomenclature for this instrument is
MS/MS, or tandem mass spectrometry. Please change tandem-MS to MS/MS
and define the abbreviation.
4) Do not forget to add fasting, infection, and viral illnesses as common causes
for MCAD decompensation. Note that the catabolic triggers you list in the first
paragraph on p.1 are usually found in adult patients, while clinical manifestations
of MCAD deficiency more commonly occur during childhood during a period of
fasting due to emesis or illness.
5) The second to last line of first paragraph, p.1. Change "turn our to be.." to
"turned out to be..."
6) The common MCAD deficiency allele is c.985A>G. Note that your
nomenclature K 304 E is for the processed enzyme and the spaces are not
needed. Due to confusion about mutations that could occur in the mitochondrial
targeting sequence (would they be called K -10 E?), we use the full length
peptide nomenclature, and the common MCAD missense mutation is p.K329E.
7) "Family moved town" vs. "family moved out of town." American English
speakers prefer the second.
8) ECG, may need to be defined in your list of abbreviations.
9) "dried blood" vs. a "dried blood spot"
10) elevation vs. elevations
11) creatinekinase vs. creatine kinase
12) creatinkinase vs. creatine kinase
13) MCAD deficiency as a "trigger" of macro-AST. Please remove the discussion
surrounding the hypothesis of MCAD deficiency leading to macro-AST formation.
It has nothing in addition to add. There is no evidence in the literature of this
occurrence, nor am I aware of a macro-AST observed in >2,500 MCAD
deficiency cases diagnosed by MS/MS newborn screening to date (based on an
international registry). Thus, it is a rare observation, likely related to an immune
response.
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests