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JIMD Reports Volume 16 pp 51–56Cite as

Reversal of Respiratory Failure in Both Neonatal and Late Onset Isolated Remethylation Disorders

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Part of the book series: JIMD Reports ((JIMD,volume 16))

Abstract

Respiratory failure is a well-documented potential presentation of inherited isolated remethylation disorders (IRDs). It appears to be a combination of both central and peripheral neuropathy and has previously often been considered to herald an irreversible neurological decline. We present three patients, one with methionine synthase (cblG) and two with methyltetrahydrofolate reductase deficiency (MTHFR). One patient with MTHFR presented in infancy, and other patients in later childhood. All three patients required intubation for respiratory failure but in all three, this was totally reversed by the initiation of medical therapy. This consisted of betaine and folinic acid supplementation in all three, methionine in two and cobalamin supplementation in two. The rate of respiratory improvement was variable, though two of the cases were successful extubated within a week of commencement of medical therapy. We document their subsequent clinical, biochemical and electrophysiological progress and review the potential pathological mechanisms underlying respiratory failure in these disorders.

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Acknowledgements

The authors would like to acknowledge the contribution of Professor B Fowler and the University Children’s hospital Zurich for the fibroblast work on patients 1 and 2 and Dr Rodenburg and Prof Van Den Heuvel at the Stichting klinisc- Genetisch Centrum Nijmegen for their work on patient 3.

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Authors and Affiliations

  1. Metabolic Medicine Unit, Great Ormond Street Hospital for Children with UCL Institute of Child Health, London, UK

    A. Broomfield, L. Abulhoul & M. Cleary

  2. Department of Neurophysiology, Great Ormond Street Hospital for Children with UCL Institute of Child Health, London, UK

    W. Pitt

  3. Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, St Mary’s Hospital, Oxford Road, Manchester, M13 9WL, UK

    E. Jameson

Authors
  1. A. Broomfield
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  2. L. Abulhoul
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  3. W. Pitt
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  4. E. Jameson
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  5. M. Cleary
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Corresponding author

Correspondence to A. Broomfield .

Editor information

Editors and Affiliations

  1. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  2. WSU Division of Health Sciences Clinical Pharmacology Unit, Spokane, Washington, USA

    K. Michael Gibson

  3. Department of Biochemistry Genetics Unit, University of Oxford, Oxford, United Kingdom

    Garry Brown

  4. Department of Pediatrics IGMD, Tulane University Medical School Hayward Genetics Center, New Orleans, Louisiana, USA

    Eva Morava

  5. Heidelberg University Hospital Centre for Child & Adolescent Med, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Garry Brown

Appendices

Synopsis

Acute respiratory failure seen in remethylation disorders is multifactorial but with aggressive medical management can be reversed.

Compliance with Ethics Guidelines

Alexander Broomfield, Lara Abulhoul, Matthew Pitt, Elisabeth Jameson and Maureen Cleary declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.

Contributions of Each Author

Dr Broomfield conception and design of study, draft article. Dr Abulhoul revision of article and collection of data. Dr Jameson design of article and revision. Dr Pitt analysis and interpretation of data. Dr Cleary revision of article and provision of data.

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© 2014 SSIEM and Springer-Verlag Berlin Heidelberg

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Broomfield, A., Abulhoul, L., Pitt, W., Jameson, E., Cleary, M. (2014). Reversal of Respiratory Failure in Both Neonatal and Late Onset Isolated Remethylation Disorders. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports Volume 16. JIMD Reports, vol 16. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_319

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  • DOI: https://doi.org/10.1007/8904_2014_319

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-44586-0

  • Online ISBN: 978-3-662-44587-7

  • eBook Packages: MedicineMedicine (R0)

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