International Meeting for Autism Research: Distinct Profile of Glutamate, Leucine, and Polar Neutral Amino Acids In Children with Autism Spectrum Disorders

Distinct Profile of Glutamate, Leucine, and Polar Neutral Amino Acids In Children with Autism Spectrum Disorders

Thursday, May 12, 2011
Elizabeth Ballroom E-F and Lirenta Foyer Level 2 (Manchester Grand Hyatt)
2:00 PM
T. V. Obukhanych1, R. Tirouvanziam2, J. Laval2, P. A. Aronov3, R. A. Libove4, A. Goswami4, K. J. Parker4, R. O'Hara4, L. Herzenberg1, L. Herzenberg1 and A. Y. Hardan4, (1)Department of Genetics, Stanford University School of Medicine, Stanford, CA, (2)Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, (3)Vincent Coates Mass Spectrometry Laboratory, Stanford University, Stanford, CA, (4)Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA
Background: Autism Spectrum Disorders (ASD) are heterogeneous neurodevelopmental disorders of unknown etiology affecting social, communication, cognitive, and behavioral skills.  Preliminary studies suggest that amino acid (AA) balance in the brain may be implicated in the pathophysiology of ASD.

Objectives: The goals of this study were: (i) to determine whether children with ASD have altered levels of plasma AA compared to neuro-typically developing (NT) children; (ii) to assess differences in developmental regulation of plasma AA levels between children with ASD and NT children; (iii) to examine correlations between plasma AA levels and clinical features in children with ASD; and (iv) to determine whether children with ASD can be distinguished from NT children based on their plasma AA profile. 

Methods: Twenty-seven children with ASD and 20 unrelated age-matched NT children were recruited for this study.  ASD diagnosis was based on the Autism Diagnostic Interview-Revised, the Autism Diagnostic Observation Schedule, and expert clinical opinion.  Behavioral characterization included the Social Responsiveness Scale and the Sensory Profile Questionnaire.  Levels of 20 AA were measured in platelet-poor plasma fraction prepared by dual centrifugation.  A quantitative liquid chromatography-mass spectrometry method based on optimized AA separation and derivatization was used to ensure increased sensitivity and reliability of AA measurements.

 Results:   After controlling for multiple comparisons, levels of glutamine, threonine, asparagine, citrulline, serine, and tyrosine (all of which are polar neutral AA), and of the essential AA leucine were lower in the ASD group when compared to the control group (P<.0025 for all).  Glutamate was the only AA, for which levels were slightly higher in the ASD group when compared to the control group (P=.02), although the difference did not reach statistical significance per our stringent statistical criteria.  A lack of the typical decrease of glutamate (and aspartate) with age was found in the ASD group.  In contrast, a non-typical increase with age for isoleucine and lysine was observed.  Associations were identified between plasma levels of glutamate, leucine, serine, and asparagine and clinical features involving sensory deficits.  Finally, glutamine levels yielded high predictive values for discriminating between children with ASD and NT children, either alone or in combination with other polar neutral AA (area under the receiver operating characteristics curve of .87 versus .92-.96, P<.0001 for all).

Conclusions: Preliminary findings from this pilot study suggest that children with ASD might have reduction in plasma levels of most polar neutral AA as well as leucine.  This AA profile appears to distinguish ASD from NT subjects.  Future studies, including larger cohorts, are warranted to confirm these findings.

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