A severe form of autosomal recessive spinocerebellar ataxia associated with novel PMPCA variants

Yoko Takahashi, Masaya Kubota, Rika Kosaki, Kenjiro Kosaki, Akira Ishiguro; Brain and Development, Volume 43, Issue 3, 2021, Pages 464-469, doi:10.1016/j.braindev.2020.11.008. 

Spinocerebellar ataxia, autosomal recessive 2 (SCAR2) [MIM:213200] is a rare autosomal recessive disease of spinocerebellar ataxia associated with degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR2 is characterized by onset of impaired motor development and ataxic gait in early childhood. Recently, several PMPCA gene variants have been reported in SCAR2 patients with mild and non-progressive symptoms. PMPCA codes frataxin, which is crucial for iron biosynthesis in cells. 

**Evidences showed that MPP ( Mitochondrial-processing peptidase subunit alpha) is an enzyme that in humans is encoded by the PMPCA gene, it's involved in the proteolytic maturation of Frataxin, a protein responsible for iron homeostasis. Accordingly, MPP deficiency was shown to be involved in Friedreich ataxia, an autossomic recessive neurodegenerative disorder.

Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

Prof Kathrin Reetz, MD, Imis Dogan, PhD, Prof Ralf-Dieter Hilgers, PhD, Prof Paola Giunti, MD, Michael H Parkinson, MBBS, Caterina Mariotti, MD, Lorenzo Nanetti, MD, Prof Alexandra Durr, MD, Claire Ewenczyk, MD, Sylvia Boesch, MDWolfgang Nachbauer, MD, Thomas Klopstock, MD,, Claudia Stendel, MD, Francisco Javier Rodríguez de Rivera Garrido, MD, Christian Rummey, PhD, Prof Ludger Schöls, MD, Stefanie N Hayer, PhD Prof Thomas Klockgether, MD, Ilaria Giordano, MD, Claire Didszun, PhD, Myriam Rai, PhD, Prof Massimo Pandolfo, MD, Prof Jörg B Schulz on behalf of theEFACTS study group; The Lancet Neurology, Published:March 23, 2021 DOI:10.1016/S1474-4422(21)00027-2 

The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia.