Novel proton MR spectroscopy findings in adenylosuccinate lyase deficiency

Authors

  • Maria Zulfiqar MD,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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    • Equally contributed to the manuscript.

  • Doris D.M. Lin MD, PhD,

    Corresponding author
    1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    • Russel H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 600 North Wolfe St., Phipps B-100, Baltimore, MD 21287
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    • Equally contributed to the manuscript.

  • Marinette Van der Graaf PhD,

    1. Department of Pediatrics, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
    2. Department of Radiology, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
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  • Peter B. Barker DPhil,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, USA
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    • Equally contributed to the manuscript.

  • Jill A. Fahrner MD, PhD,

    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Sandrine Marie PhD,

    1. Laboratory of Physiological Chemistry, Christian de Duve Institute of Cellular Pathology and Universite Catholique de Louvain, Brussels, Belgium
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  • Eva Morava MD, PhD,

    1. Department of Pediatrics, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
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  • Lonneke De Boer PhD,

    1. Department of Pediatrics, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
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  • Michel A.A.P. Willemsen MD,

    1. Department of Pediatric Neurology, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
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  • Eileen Vining MD,

    1. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. John M. Freeman Pediatric Epilepsy Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    3. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Alena Horská PhD,

    1. Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • Udo Engelke PhD,

    1. Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Institute of Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
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  • Ron A. Wevers PhD,

    1. Laboratory of Genetic, Endocrine and Metabolic Diseases, Department of Laboratory Medicine, Institute of Genetic and Metabolic Disease, Radboud University Nijmegen Medical Centre (RUNMC), Nijmegen, The Netherlands
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    • Equally contributed to the manuscript.

  • Gustavo H.B. Maegawa MD, PhD

    1. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    2. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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    • Equally contributed to the manuscript.


Abstract

Adenylosuccinate lyase (ADSL) deficiency is a rare inborn error of metabolism resulting in accumulation of metabolites including succinylaminoimidazole carboxamide riboside (SAICAr) and succinyladenosine (S-Ado) in the brain and other tissues. Patients with ADSL have progressive psychomotor retardation, neonatal seizures, global developmental delay, hypotonia, and autistic features, although variable clinical manifestations may make the initial diagnosis challenging. Two cases of the severe form of the disease are reported here: an 18-month-old boy with global developmental delay, intractable neonatal seizures, progressive cerebral atrophy, and marked hypomyelination, and a 3-month-old girl presenting with microcephaly, neonatal seizures, and marked psychomotor retardation. In both patients in vivo proton magnetic resonance spectroscopy (MRS) showed the presence of S-Ado signal at 8.3 ppm, consistent with a prior report. Interestingly, SAICAr signal was also detectable at 7.5 ppm in affected white matter, which has not been reported in vivo before. A novel splice-site mutation, c.IVS12 + 1/G > C, in the ADSL gene was identified in the second patient. Our findings confirm the utility of in vivo proton MRS in suggesting a specific diagnosis of ADSL deficiency, and also demonstrate an additional in vivo resonance (7.5 ppm) of SAICAr in the cases of severe disease. J. Magn. Reson. Imaging 2013;37:974–980. © 2012 Wiley Periodicals, Inc.

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