Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-57003
Adamsen, D; Meili, D; Blau, N; Thöny, B; Ramaekers, V (2011). Autism associated with low 5-hydroxyindolacetic acid in CSF and the heterozygous SLC6A4 gene Gly56Ala plus 5-HTTLPR L/L promoter variants. Molecular Genetics and Metabolism, 102(3):368-373.
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The known Gly56Ala mutation in the serotonin transporter SERT (or 5-HTT), encoded by the SLC6A4 gene, causes increased serotonin reuptake and has been associated with autism and rigid-compulsive behavior. We report a patient with macrocephaly from birth, followed by hypotonia, developmental delay, ataxia and a diagnosis of atypical autism (PDD-NOS) in retrospect at the age of 4½years. Low levels of the serotonin end-metabolite 5-hydroxyindolacetic acid (5HIAA) in CSF were detected, and SLC6A4 gene analysis revealed the heterozygous Gly56Ala alteration and the homozygous 5-HTTLPR L/L promoter variant. These changes are reported to be responsible for elevated SERT activity and expression, suggesting that these alterations were responsible in our patient for low serotonin turnover in the central nervous system (CNS). Daily treatment with 5-hydroxytryptophan (and carbidopa) led to clinical improvement and normalization of 5HIAA, implying that brain serotonin turnover normalized. We speculate that the mutated 56Ala SERT transporter with elevated expression and basal activity for serotonin re-uptake is accompanied with serotonin accumulation within pre-synaptic axons and their vesicles in the CNS, resulting in a steady-state of lowered serotonin turnover and degradation by monoamine-oxidase (MAO) enzymes in pre-synaptic or neighboring cells.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic|
04 Faculty of Medicine > Center for Integrative Human Physiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||26 Feb 2012 12:29|
|Last Modified:||09 Dec 2012 16:38|
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