Abstract
Background: Lesch–Nyhan disease (LND) is an X-chromosomal disorder of purine metabolism characterized by hyperuricemia, dystonia, and self-mutilation, leading to an extremely high burden of disease in affected patients and families. Although allopurinol therapy can control hyperuricemia, it has no effect on self-mutilation and neurological symptoms. Single reports describe a beneficial effect of S-adenosylmethionine (SAM) on the neurological symptoms, which motivated us to evaluate this alternative treatment.
Methods: We performed a double-blind placebo-controlled trial to analyze the effects of SAM on self-mutilation attempts in a male patient affected by LND. The trial lasted for 282 days and comprised three alternating verum and placebo periods of 50 days each. The mother of the patient recorded attempts of self-mutilation during the entire trial.
Results: While verum and placebo were both well tolerated, a total of 1,762 events of self-mutilation were recorded, of which 1,281 events were in the placebo period and 481 in the verum period. The daily mean of events was 8.6 with placebo and 4.5 with SAM corresponding to a 50 % decrease in self-mutilation events under SAM treatment (p < 0.05).
Conclusion: The results of this double-blind placebo-controlled single-case trial suggest that SAM can have a beneficial effect on self-mutilation in patients with LND, possibly by replenishing the purine pool in affected brain cells.
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Acknowledgments
We appreciate the help of the family of our patient in conducting this trial and specifically the excellent recording of self-mutilation events. We also thank Mrs. Ursina Spörri, Zurich, for her help in data analysis.
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Communicated by: Pascale de Lonlay
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Matthias Lauber, Barbara Plecko, Miriam Pfiffner, Jean-Marc Nuoffer, and Johannes Häberle declare that they have no conflict of interest.
This article does contain studies with a human subject. The patient received a medication as compassionate use after approval was obtained from the SwissMedic/Schweizerisches Heilmittelinstitut. As this was a therapeutic trial with a licensed drug in a single patient, there was no need to obtain formal approval by the local ethical board.
Jean-Marc Nuoffer and Johannes Häberle have together planned the study that was performed under the supervision of Johannes Häberle. Analysis and interpretation of data, drafting of the article, and revision were performed by Matthias Lauber, Barbara Plecko, Miriam Pfiffner, Jean-Marc Nuoffer, and Johannes Häberle.
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Lauber, M., Plecko, B., Pfiffner, M., Nuoffer, JM., Häberle, J. (2016). The Effect of S-Adenosylmethionine on Self-Mutilation in a Patient with Lesch–Nyhan Disease. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 32. JIMD Reports, vol 32. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2016_571
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DOI: https://doi.org/10.1007/8904_2016_571
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