Treatment of Lesch-Nyhan disease with S-adenosylmethionine: experience with five young Malaysians, including a girl

Chen, Bee C., Balasubramaniam, Shanti, McGown, Ivan N., O'Neill, J. Patrick, Chng, Gaik S., Keng, Wee T., Ngu, Lock H. and Duley, John A. (2013) Treatment of Lesch-Nyhan disease with S-adenosylmethionine: experience with five young Malaysians, including a girl. Brain and Development, 36 7: 593-600. doi:10.1016/j.braindev.2013.08.013

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Author Chen, Bee C.
Balasubramaniam, Shanti
McGown, Ivan N.
O'Neill, J. Patrick
Chng, Gaik S.
Keng, Wee T.
Ngu, Lock H.
Duley, John A.
Title Treatment of Lesch-Nyhan disease with S-adenosylmethionine: experience with five young Malaysians, including a girl
Journal name Brain and Development   Check publisher's open access policy
ISSN 0387-7604
Publication date 2013-09-18
Sub-type Article (original research)
DOI 10.1016/j.braindev.2013.08.013
Volume 36
Issue 7
Start page 593
End page 600
Total pages 8
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2014
Language eng
Formatted abstract
Background: Lesch–Nyhan disease (LND) is a rare X-linked recessive neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine phosphoribosyltransferase (HPRT, EC which is responsible for recycling purine bases into purine nucleotides. Affected individuals have hyperuricemia leading to gout and urolithiasis, accompanied by a characteristic severe neurobehavioural phenotype with compulsive self-mutilation, extrapyramidal motor disturbances and cognitive impairment.

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.
Keyword Lesch–Nyhan disease
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 18 September 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Pharmacy Publications
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Citation counts: TR Web of Science Citation Count  Cited 5 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 01 Oct 2013, 14:50:40 EST by Myrtle Sahabandu on behalf of School of Pharmacy