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January 25, 2010

Elevated CSF N-acetylaspartylglutamate in patients with free sialic acid storage diseases

F. Mochel, MD, U.F.H. Engelke, PhD, J. Barritault, BS, B. Yang, MD, N. H. McNeill, MS, J. N. Thompson, PhD, A. Vanderver, MD, … Show All … , N. I. Wolf, MD, M. A. Willemsen, MD, PhD, F. W. Verheijen, PhD, F. Seguin, PhD, R. A. Wevers, PhD, and R. Schiffmann, MDAuthors Info & Affiliations
January 26, 2010 issue
74 (4) 302-305
https://doi.org/10.1212/WNL.0b013e3181cbcdc4
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Abstract

Objective: To investigate body fluids of patients with undiagnosed leukodystrophies using in vitro 1H-NMR spectroscopy (H-NMRS).
Methods: We conducted a cross-sectional study using high-resolution in vitro H-NMRS on CSF and urine samples.
Results: We found a significant increase of free sialic acid in CSF or urine in 6 of 41 patients presenting with hypomyelination of unknown etiology. Molecular genetic testing revealed pathogenic mutations in the SLC17A5 gene in all 6 patients. H-NMRS revealed an increase of N-acetylaspartylglutamate in the CSF of all patients with SLC17A5 mutation (range 13–114 μmol/L, reference <12 μmol/L).
Conclusion: In patients with undiagnosed leukodystrophies, increased free sialic acid in CSF or urine is a marker for free sialic acid storage disorder and facilitates the identification of the underlying genetic defect. Because increase of N-acetylaspartylglutamate in CSF has been observed in other hypomyelinating disorders, it can be viewed as a marker of a subgroup of hypomyelinating disorders.

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Information & Authors

Information

Published In

Neurology®
Volume 74 • Number 4 • January 26, 2010
Pages: 302-305
PubMed: 20101035

Copyright

© 2010.

Publication History

Published online: January 25, 2010
Published in print: January 26, 2010

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Authors

Affiliations & Disclosures

F. Mochel, MD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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U.F.H. Engelke, PhD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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J. Barritault, BS
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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B. Yang, MD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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N. H. McNeill, MS
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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J. N. Thompson, PhD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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A. Vanderver, MD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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N. I. Wolf, MD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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M. A. Willemsen, MD, PhD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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F. W. Verheijen, PhD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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F. Seguin, PhD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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R. A. Wevers, PhD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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R. Schiffmann, MD
From the Institut National de la Santé et de la Recherche Médicale (INSERM) UMR S975 (F.M.), Hôpital de La Salpêtrière, Paris, France; Institute of Metabolic Diseases (F.M., B.Y., N.H.M., R.S.), Baylor Research Institute, Dallas, TX; Laboratory of Pediatrics and Neurology (U.F.H.E., R.A.W.) and Department of Pediatric Neurology (M.A.W.), Radboud University Nijmegen Medical Center, The Netherlands; INSERM U927 (J.B., F.S.), Université de Poitiers, Hôpital La Milêtrie, France; Department of Genetics (J.N.T.), University of Alabama, Birmingham, AL; Children's National Medical Center (A.V.), Children's Research Institute, Center for Genetic Medicine, Washington, DC; Department of Child Neurology (N.I.W.), VU University Medical Center, Amsterdam, The Netherlands; and Department of Clinical Genetics (F.W.V.), Erasmus Medical Center, Rotterdam, The Netherlands.
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Notes

Address correspondence and reprint requests to Dr. Fanny Mochel, INSERM UMR S975, Hôpital de La Salpêtrière, 47 Bld de l'Hôpital, Bâtiment Nouvelle Pharmacie–4ème étage, 75013 Paris, France[email protected]

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