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From the MRC Biochemical and Clinical Magnetic Resonance Unit (Drs. Rae, Dixon, Blamire, Thompson, Styles, and Radda), John Radcliffe Hospital, Oxford; the MRC Cognitive Development Unit (Dr. Karmiloff-Smith and J. Grant), London; the Institute of Child Health (Dr. Karmiloff-Smith and J. Grant), University College London; the Department of Clinical Neurology(Dr. Lee), The Radcliffe Infirmary, Oxford, UK; and the Department of Biochemistry (Drs. Rae and Thompson), The University of Sydney, Australia.
Address correspondence and reprint requests to Dr. Caroline Rae, Dept of Biochemistry, The University of Sydney, 2006, Australia.
Objective: To determine what biochemical changes may occur in the brain in Williams syndrome (WS) and whether these changes may be related to the cognitive deficits.
Background: WS is a rare, congenital disorder with a characteristic physical, linguistic, and behavioral phenotype with known cognitive deficits.
Methods: We obtained 31P magnetic resonance spectra (MRS) from a region consisting of mostly frontal and parietal lobe of 14 patients with WS (age, 8 to 37 years) and 48 similarly-aged controls. 1H MRS (27 cm3) localized to the left cerebellum obtained from the WS cohort were compared with those from 16 chronological age- and sex-matched normal controls. A battery of cognitive tests were administered to all subjects undergoing1 H MRS.
Results: WS brains exhibited significant biochemical abnormalities. All31 P MRS ratios containing the phosphomonoester (PME) peak were significantly altered in WS, suggesting that PME is significantly decreased. Ratios of choline-containing compounds and creatine-containing compounds to N-acetylaspartate (Cho/NA and Cre/NA) were significantly elevated in the cerebellum in WS cf. controls, whereas the ratio of Cho/Cre was not altered. This suggests a decrease in the neuronal marker N-acetylaspartate in the cerebellum. Significant correlations were found between the cerebellar ratios Cho/NA and Cre/NA and the ability of all subjects at various neuropsychological tests, including Verbal and Performance IQ, British Picture Vocabulary Scale, Ravens Progressive Matrices, and Inspection Time.
Conclusions: The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.
Supported by the Medical Research Council, United Kingdom. C.R. held a(Foundation) Research Fellowship from the Faculty of Science, The University of Sydney, Australia, for part of this work and a Junior Research Fellowship from Wolfson College, Oxford.
Received December 11, 1997. Accepted in final form April 3, 1998.
This article has been cited by other articles:
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  M. Tassabehji Williams-Beuren syndrome: a challenge for genotype-phenotype correlations Hum. Mol. Genet., October 15, 2003; 12(90002): R229 - 237. [Abstract] [Full Text] [PDF]
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 P. Kaplan, P. P. Wang, and U. Francke Williams (Williams Beuren) Syndrome: A Distinct Neurobehavioral Disorder J Child Neurol, March 1, 2001; 16(3): 177 - 190. [PDF]
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 L. Chang, T. Ernst, N. Berman, C. Rae, C. Thompson, A. Karmiloff-Smith, J. Grant, M. Lee, R. M. Dixon, A. Blamire, et al. Brain biochemistry in Williams syndrome: Evidence for a role of the cerebellum in cognition? Neurology, March 1, 1999; 52(4): 894 - 894. [Full Text]
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M. L. Rossen and H. B. Sarnat Why should neurologists be interested in Williams syndrome? Neurology, July 1, 1998; 51(1): 8 - 9. [Full Text] [PDF]
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