Matthias Lauber1, Barbara Plecko2, Miriam Pfiffner3, Jean-Marc Nuoffer4,5, Johannes Häberle6. 1. Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032, Zurich, Switzerland. 2. Division of Neuropaediatrics and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032, Zurich, Switzerland. 3. Division of Pharmacy, University Children's Hospital, Steinwiesstr. 75, 8032, Zurich, Switzerland. 4. Department of Paediatrics, Inselspital, University Hospital Bern, Bern, Switzerland. 5. Institute of Clinical Chemistry, Inselspital, University Hospital Bern, Bern, Switzerland. 6. Division of Metabolism and Children's Research Center, University Children's Hospital, Steinwiesstr. 75, 8032, Zurich, Switzerland. Johannes.Haeberle@kispi.uzh.ch.
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.
RCT Entities:
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.
Authors: Bee C Chen; Shanti Balasubramaniam; Ivan N McGown; J Patrick O'Neill; Gaik S Chng; Wee T Keng; Lock H Ngu; John A Duley Journal: Brain Dev Date: 2013-09-18 Impact factor: 1.961
Authors: H A Jinnah; Irene Ceballos-Picot; Rosa J Torres; Jasper E Visser; David J Schretlen; Alfonso Verdu; Laura E Laróvere; Chung-Jen Chen; Antonello Cossu; Chien-Hui Wu; Radhika Sampat; Shun-Jen Chang; Raquel Dodelson de Kremer; William Nyhan; James C Harris; Stephen G Reich; Juan G Puig Journal: Brain Date: 2010-02-22 Impact factor: 13.501