Abstract | BACKGROUND: AIM: For its theoretical therapeutic potential to replenish the brain purine nucleotide pool, oral supplementation with S-adenosylmethionine (SAMe) was trialed in 5 Malaysian children with LND, comprising 4 related Malay children from 2 families, including an LND girl, and a Chinese Malaysian boy. RESULTS: Dramatic reductions of self-injury and aggressive behaviour, as well as a milder reduction of dystonia, were observed in all 5 patients. Other LND neurological symptoms did not improve during SAMe therapy. DISCUSSION: Molecular mechanisms proposed for LND neuropathology include GTP depletion in the brain leading to impaired dopamine synthesis, dysfunction of G-protein-mediated signal transduction, and defective developmental programming of dopamine neurons. The improvement of our LND patients on SAMe, particularly the hallmark self-injurious behaviour, echoed clinical progress reported with another purine nucleotide depletion disorder, Arts Syndrome, but contrasted lack of benefit with the purine disorder adenylosuccinate lyase deficiency. This first report of a trial of SAMe therapy in LND children showed remarkably encouraging results that warrant larger studies.
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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 & development
(Brain Dev)
Vol. 36
Issue 7
Pg. 593-600
(Aug 2014)
ISSN: 1872-7131 [Electronic] Netherlands |
PMID | 24055166
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- Purines
- S-Adenosylmethionine
- purine
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Topics |
- Adolescent
- Aggression
(drug effects)
- Child
- Child, Preschool
- Dystonia
(drug therapy)
- Female
- Humans
- Infant
- Lesch-Nyhan Syndrome
(drug therapy)
- Malaysia
- Male
- Pedigree
- Purines
(metabolism)
- S-Adenosylmethionine
(therapeutic use)
- Self-Injurious Behavior
(drug therapy)
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