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