title: SPG11 spastic paraplegia. A new cause of juvenile parkinsonism.
abstract: Autosomal recessive hereditary spastic paraplegia (AR HSP) with thin corpus callosum (TCC) is a rare neurodegenerative disorder often caused by mutations in the gene encoding for spatacsin at the SPG11 locus on chromosome 15q. The disease is characterized by progressive spastic paraparesis and mental retardation which occur during the first two decades of life and frequently with peripheral neuropathy. Brain magnetic resonance imaging (MRI) reveals typical TCC with periventricular white matter changes. We describe two patients, of Turkish descent, from the same consanguineous family and affected with SPG11 in association with unusual early-onset parkinsonism. Parkinsonism occurred during the very early stages of SPG11 in both patients, being in one the inaugural symptom of the disease presented as a resting tremor with akinesia, rigidity and expressing an initial moderate levodopa-response that progressively weakened. The second patient presented a resting tremor with mild akinesia and no levodopa-response. Both patients were affected with progressive spastic paraparesis which had initially occurred at 15 and 12 years of age, respectively, in association with mild mental retardation and an axonal polyneuropathy. TCC with periventricular white matter changes (PWMC) was evident by MRI and (123)I-ioflupane SPECT was abnormal. Genetic analysis detected for both patients a new c.704_705delAT, p.H235RfsX12 homozygous mutation in SPG11. This report provides evidence that parkinsonism may initiate SPG11-linked HSP TCC and that SPG11 may cause juvenile parkinsonism.
authors.affiliation: Dépt. de Neurologie, Hôpital Civil, Centre Hospitalier Universitaire de Strasbourg 1, place de l'Hôpital, 67000 Strasbourg, France. anheim@titus.u-strasbg.fr
authors.forename: Mathieu
authors.initials: M
authors.lastname: Anheim
authors.forename: Clotilde
authors.initials: C
authors.lastname: Lagier-Tourenne
authors.forename: Giovanni
authors.initials: G
authors.lastname: Stevanin
authors.forename: Marie
authors.initials: M
authors.lastname: Fleury
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.forename: Izzie Jacques
authors.initials: IJ
authors.lastname: Namer
authors.forename: Paola
authors.initials: P
authors.lastname: Denora
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010264:Paraplegia / Q000235:genetics* / Q000473:pathology; D020734:Parkinsonian Disorders / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*
chemical_list: D011506:Proteins; C520412:SPG11 protein, human