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This could be offtopic because this might be just a case of sloppy phrasing and a case of "asking to guess what the authors really meant". A quote from an abstract (GTP-cyclohydrolase deficiency responsive to sapropterin and 5-HTP supplementation: relief of treatment-refractory depression and suicidal behaviour):

Our hope is that other patients presenting with treatment-refractory, life-threatening depression will be evaluated for defects in this pathway. A brief summary of the scientific bases for selecting the replacement therapies is included. For future research, we propose that potential pharmacogenetic characterisation might also be evaluated so that these ‘rare’ syndromes are treated, if possible, at an earlier age.

Besides the fact that "characterization" cannot be "evaluated", I can't understand how assessing the pharmacogenetics of sapropterin or some other drug (?) could help treat the syndrome at an earlier age. What exactly do the authors mean?

My guess is that they mean that "some drug used on the patient could cause this syndrome in some yet unknown way". I base my guess on this passage from the text (free full text is available):

The metabolic profile reported here is unique to GTPCH deficiency or a defect in the GTP activator protein. While there is no known demonstrated defect in this protein, it would cause similar functional deficiency. Other enzymatic defects in the pterin synthetic pathway present with very different metabolic profiles. It should be noted that little is known about alterations or responses in this pathway with neuroactive metabolic agents. For example, there could be non-specific secondary changes mimicking deficiencies that are not clinically relevant. Alterations in the pathway could be related to a pathophysiologic process or even pharmacotherapy.

Am I right? Or maybe we should read "genetics" instead of "pharmacogenetics" - this could make the phrase clear in the sense that "we should get to the genetic roots of these syndromes"? In this case, all seemingly becomes understandable.

  • I do not think this can be definitively answered, only speculated, unless we get the author to respond. However, pharmacogenetics in this setting generally means examining an individual's genotypes of pathways like the liver cytochromes responsible for processing a representative sample of medications, which can tell if they are more likely to rapidly or slowly metabolize medications (--> decreased efficacy or increased side effects). – DoctorWhom Mar 18 '19 at 10:20
  • I think in this case, the hope is in the future that we can identify which treatments are more likely to be successful earlier in the disease course, at an earlier age, to reduce the amount of time they are "resistant." Again, this is speculative, so please poke me for answering in the comments if I should have placed this in the answers! – DoctorWhom Mar 18 '19 at 10:24

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