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Mitochondrial membrane protein associated neurodegenration: A novel variant of neurodegeneration with brain iron accumulation

Authors

  • Eva C. Schulte MD,

    1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
    2. Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
    3. Institut für Humangenetik, Klinikum recht der Isar, Technische Universität München, Munich, Germany
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    • Eva C. Schulte and Malte C. Claussen contributed equally to the article.

  • Malte C. Claussen MD,

    1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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    • Eva C. Schulte and Malte C. Claussen contributed equally to the article.

  • Angela Jochim MD,

    1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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  • Tobias Haack MD,

    1. Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
    2. Institut für Humangenetik, Klinikum recht der Isar, Technische Universität München, Munich, Germany
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  • Monika Hartig MD,

    1. Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
    2. Institut für Humangenetik, Klinikum recht der Isar, Technische Universität München, Munich, Germany
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  • Maja Hempel MD,

    1. Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
    2. Institut für Humangenetik, Klinikum recht der Isar, Technische Universität München, Munich, Germany
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  • Holger Prokisch PhD,

    1. Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
    2. Institut für Humangenetik, Klinikum recht der Isar, Technische Universität München, Munich, Germany
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  • Ursula Haun-Jünger MD,

    1. Sozialpädiatrisches Zentrum, Klinikum Bremen-Mitte, Bremen, Germany
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  • Juliane Winkelmann MD,

    1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
    2. Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany
    3. Institut für Humangenetik, Klinikum recht der Isar, Technische Universität München, Munich, Germany
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  • Bernhard Hemmer MD,

    1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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  • Annette Förschler MD,

    1. Abteilung für Neuroradiologie, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
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  • Rüdiger Ilg MD

    Corresponding author
    1. Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
    • Correspondence to: Rüdiger Ilg, Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 Munich, Germany; ilg@lrz.tum.de

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  • Funding agencies: This study was financed exclusively by in-house funding from the Neurologische Klinik & Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

  • Relevant conflicts of interest/financial disclosures: Holger Prokisch receives research support from the Impulse and Networking Fund of the Helmholtz Association within the framework of the Helmholtz Alliance for Mental Health in an Ageing Society (HA-215) and the German Federal Ministry of Education and Research (BMBF)–funded German Center for Diabetes Research (DZD e.V.), Systems Biology of Metabotypes grant (SysMBo 0315494A), and the German Network for Mitochondrial Disorders (mitoNET 01GM0867). Rüdiger Ilg is supported by the medical faculty of the Technische Universität München (KKF).

  • Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Background

Recently, mutations in an open-reading frame on chromosome 19 (C19orf12) were identified as a novel genetic factor in neurodegeneration with brain iron accumulation (NBIA). Because of the mitochondrial localization of the derived protein, this variant is referred to as mitochondrial membrane protein-associated neurodegeneration with brain iron accumulation (MPAN).

Methods/Results

We describe the clinical phenotype and MRI of 3 newly identified individuals with MPAN due to either previously reported or novel homozygous or compound heterozygous genetic alterations in C19orf12.

Conclusions

MPAN is characterized by a juvenile-onset, slowly progressive phenotype with predominant lower limb spasticity, generalized dystonia, and cognitive impairment. Typical additional features include axonal motor neuropathy and atrophy of the optic nerve. MRI showed iron deposition in the globus pallidus and substantia nigra without the eye-of-the-tiger sign, which is typical for PKAN, the most frequent form of NBIA. © 2012 Movement Disorder Society

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