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New Cases of DHTKD1 Mutations in Patients with 2-Ketoadipic Aciduria

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JIMD Reports, Volume 25

Part of the book series: JIMD Reports ((JIMD,volume 25))

Abstract

2-Ketoadipic aciduria (OMIM 204750), a defect in the catabolic pathway of tryptophan, lysine, and hydroxylysine, is characterized by elevations in 2-ketoadipic, 2-aminoadipic, and 2-hydroxyadipic acids. Patients with the aforementioned biochemical profile have been described with a wide range of clinical presentations, from early-onset developmental delay, epilepsy, ataxia, and microcephaly to completely normal. This broad range of phenotypes has led some to question whether 2-ketoadipic aciduria represents a true disease state or if the biochemical abnormalities found in these patients merely reflect an ascertainment bias. We present four additional individuals from two families, with 2-ketoadipic aciduria with compound heterozygous or homozygous mutations in DHTKD1, three of which remain asymptomatic.

Competing interests: None declared

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Acknowledgments

We thank the families for their steadfast commitment to participate in this study, the generous support of the Fry Family Foundation to CHOC Children’s Metabolic Program, and Dr. Bridget Wilcken for her cooperation and support.

Author information

Authors and Affiliations

  1. Division of Metabolic Disorders, CHOC Children’s Hospital, Orange, CA, USA

    Ashlee R. Stiles & Jose E. Abdenur

  2. Anschutz Medical Campus and Children’s Hospital Colorado, University of Colorado at Denver, Aurora, CO, USA

    Leah Venturoni, Michael Woontner & Stephen Goodman

  3. Division of Psychology, CHOC Children’s Hospital, Orange, CA, USA

    Grace Mucci

  4. Division of Neurology, CHOC Children’s Hospital, Orange, CA, USA

    Naser Elbalalesy

  5. Department of Pediatrics, University of California Irvine, Irvine, CA, USA

    Jose E. Abdenur

Authors
  1. Ashlee R. Stiles
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  2. Leah Venturoni
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  3. Grace Mucci
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  4. Naser Elbalalesy
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  5. Michael Woontner
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  6. Stephen Goodman
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  7. Jose E. Abdenur
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Corresponding author

Correspondence to Jose E. Abdenur .

Editor information

Editors and Affiliations

  1. Tulane University Medical School , New Orleans, Louisiana, USA

    Eva Morava

  2. Division of Metabolism and Children’s Re, University Children's Hospital Zurich, Zurich, Switzerland

    Matthias Baumgartner

  3. Division of Child and Adolescent Neurolo, Mayo Clinic, Rochester, Minnesota, USA

    Marc Patterson

  4. Clinical and Molecular Genetics Unit, UCL Institute of Child Health, London, UK

    Shamima Rahman

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

    Johannes Zschocke

  6. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Baden-Württemberg, Germany

    Verena Peters

Additional information

Communicated by: Nenad Blau, PhD

Appendices

Synopsis

Our paper highlights that while genetic abrogation of DHTKD1 leads to the accumulation of 2-ketoadipic, 2-aminoadipic, and 2-hydroxyadipic acids resulting in a biochemical diagnosis of 2-ketoadipic aciduria, this disruption does not always result in an observed clinical phenotype.

Compliance with Ethics Guidelines

Conflict of Interest

Ashlee Stiles, Leah Venturoni, Grace Mucci, Michael Woontner, Stephen Goodman, and Jose Abdenur declare that they have no conflict of interest.

Informed Consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Animal Rights

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

Contributions of Individual Authors

Ashlee Stiles and Leah Venturoni contributed equally to the manuscript. Each helped to draft the case report presented.

Grace Mucci performed all neuropsychological testing and provided detailed summary of the data for the case report.

Naser Elbalalesy provided direct patient care, performed neurological examinations, and interpreted neurology test results.

Michael Woontner helped to perform data analysis of WES and edited the manuscript to provide critical feedback.

Steve Goodman and Jose Abdenur contributed equally to the manuscript. Each helped to interpret the biochemical test results and draft and review the case report providing critical feedback.

Competing Interests

The authors have no competing interests.

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© 2015 SSIEM and Springer-Verlag Berlin Heidelberg

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Stiles, A.R. et al. (2015). New Cases of DHTKD1 Mutations in Patients with 2-Ketoadipic Aciduria. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 25. JIMD Reports, vol 25. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_462

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  • DOI: https://doi.org/10.1007/8904_2015_462

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-662-49667-1

  • Online ISBN: 978-3-662-49668-8

  • eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

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